Nucleobase editors and uses thereof

Information

  • Patent Grant
  • 12344869
  • Patent Number
    12,344,869
  • Date Filed
    Monday, November 15, 2021
    3 years ago
  • Date Issued
    Tuesday, July 1, 2025
    25 days ago
Abstract
Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. In some embodiments, fusion proteins of Cas9 and nucleic acid editing proteins or protein domains, e.g., deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of Cas9 and nucleic acid editing proteins or domains, are provided.
Description
BACKGROUND OF THE INVENTION

Targeted editing of nucleic acid sequences, for example, the targeted cleavage or the targeted introduction of a specific modification into genomic DNA, is a highly promising approach for the study of gene function and also has the potential to provide new therapies for human genetic diseases.1 An ideal nucleic acid editing technology possesses three characteristics: (1) high efficiency of installing the desired modification; (2) minimal off-target activity; and (3) the ability to be programmed to edit precisely any site in a given nucleic acid, e.g., any site within the human genome.2 Current genome engineering tools, including engineered zinc finger nucleases (ZFNs),3 transcription activator like effector nucleases (TALENs),4 and most recently, the RNA-guided DNA endonuclease Cas9,5 effect sequence-specific DNA cleavage in a genome. This programmable cleavage can result in mutation of the DNA at the cleavage site via non-homologous end joining (NHEJ) or replacement of the DNA surrounding the cleavage site via homology-directed repair (HDR).6,7


One drawback to the current technologies is that both NHEJ and HDR are stochastic processes that typically result in modest gene editing efficiencies as well as unwanted gene alterations that can compete with the desired alteration.8 Since many genetic diseases in principle can be treated by effecting a specific nucleotide change at a specific location in the genome (for example, a C to T change in a specific codon of a gene associated with a disease),9 the development of a programmable way to achieve such precision gene editing would represent both a powerful new research tool, as well as a potential new approach to gene editing-based human therapeutics.


SUMMARY OF THE INVENTION

The clustered regularly interspaced short palindromic repeat (CRISPR) system is a recently discovered prokaryotic adaptive immune system10 that has been modified to enable robust and general genome engineering in a variety of organisms and cell lines.11 CRISPR-Cas (CRISPR associated) systems are protein-RNA complexes that use an RNA molecule (sgRNA) as a guide to localize the complex to a target DNA sequence via base-pairing.12 In the natural systems, a Cas protein then acts as an endonuclease to cleave the targeted DNA sequence.13 The target DNA sequence must be both complementary to the sgRNA, and also contain a “protospacer-adjacent motif” (PAM) at the 3′-end of the complementary region in order for the system to function.14


Among the known Cas proteins, S. pyogenes Cas9 has been mostly widely used as a tool for genome engineering.15 This Cas9 protein is a large, multi-domain protein containing two distinct nuclease domains. Point mutations can be introduced into Cas9 to abolish nuclease activity, resulting in a dead Cas9 (dCas9) that still retains its ability to bind DNA in a sgRNA-programmed manner.16 In principle, when fused to another protein or domain, dCas9 can target that protein to virtually any DNA sequence simply by co-expression with an appropriate sgRNA.


The potential of the dCas9 complex for genome engineering purposes is immense. Its unique ability to bring proteins to specific sites in a genome programmed by the sgRNA in theory can be developed into a variety of site-specific genome engineering tools beyond nucleases, including transcriptional activators, transcriptional repressors, histone-modifying proteins, integrases, and recombinases.11 Some of these potential applications have recently been implemented through dCas9 fusions with transcriptional activators to afford RNA-guided transcriptional activators,17,18 transcriptional repressors,16,19,20 and chromatin modification enzymes.21 Simple co-expression of these fusions with a variety of sgRNAs results in specific expression of the target genes. These seminal studies have paved the way for the design and construction of readily programmable sequence-specific effectors for the precise manipulation of genomes.


Significantly, 80-90% of protein mutations responsible for human disease arise from the substitution, deletion, or insertion of only a single nucleotide.6 Most current strategies for single-base gene correction include engineered nucleases (which rely on the creation of double-strand breaks, DSBs, followed by stochastic, inefficient homology-directed repair, HDR), and DNA-RNA chimeric oligonucleotides.22 The latter strategy involves the design of a RNA/DNA sequence to base pair with a specific sequence in genomic DNA except at the nucleotide to be edited. The resulting mismatch is recognized by the cell's endogenous repair system and fixed, leading to a change in the sequence of either the chimera or the genome. Both of these strategies suffer from low gene editing efficiencies and unwanted gene alterations, as they are subject to both the stochasticity of HDR and the competition between HDR and non-homologous end-joining, NHEJ.23-25 HDR efficiencies vary according to the location of the target gene within the genome,26 the state of the cell cycle,27 and the type of cell/tissue.28 The development of a direct, programmable way to install a specific type of base modification at a precise location in genomic DNA with enzyme-like efficiency and no stochasticity therefore represents a powerful new approach to gene editing-based research tools and human therapeutics.


Some aspects of the disclosure are based on the recognition that certain configurations of a dCas9 domain, and a cytidine deaminase domain fused by a linker are useful for efficiently deaminating target cytidine residues. Other aspects of this disclosure relate to the recognition that a nucleobase editing fusion protein with a cytidine deaminase domain fused to the N-terminus of a nuclease inactive Cas9 (dCas9) via a linker was capable of efficiently deaminating target nucleic acids in a double stranded DNA target molecule. See for example, Examples 3 and 4 below, which demonstrate that the fusion proteins, which are also referred to herein as base editors, generate less indels and more efficiently deaminate target nucleic acids than other base editors, such as base editors without a UGI domain. In some embodiments, the fusion protein comprises a nuclease-inactive Cas9 (dCas9) domain and an apolipoprotein B mRNA-editing complex 1 (APOBEC1) deaminase domain, where the deaminase domain is fused to the N-terminus of the dCas9 domain via a linker comprising the amino acid sequence SGSETPGTSESATPES (SEQ ID NO: 7). In some embodiments, the nuclease-inactive Cas9 (dCas9) domain of comprises the amino acid sequence set forth in SEQ ID NO: 263. In some embodiments, the deaminase is rat APOBEC1 (SEQ ID NO: 284). In some embodiments, the deaminase is human APOBEC1 (SEQ ID NO: 282). In some embodiments, the deaminase is pmCDA1 (SEQ ID NO: 5738). In some embodiments, the deaminase is human APOBEC3G (SEQ ID NO: 275). In some embodiments, the deaminase is a human APOBEC3G variant of any one of (SEQ ID NOs: 5739-5741).


Some aspects of the disclosure are based on the recognition that certain configurations of a dCas9 domain, and a cytidine deaminase domain fused by a linker are useful for efficiently deaminating target cytidine residues. Other aspects of this disclosure relate to the recognition that a nucleobase editing fusion protein with an apolipoprotein B mRNA-editing complex 1 (APOBEC1) deaminase domain fused to the N-terminus of a nuclease inactive Cas9 (dCas9) via a linker comprising the amino acid sequence SGSETPGTSESATPES (SEQ ID NO: 7) was capable of efficiently deaminating target nucleic acids in a double stranded DNA target molecule. In some embodiments, the fusion protein comprises a nuclease-inactive Cas9 (dCas9) domain and an apolipoprotein B mRNA-editing complex 1 (APOBEC1) deaminase domain, where the deaminase domain is fused to the N-terminus of the dCas9 domain via a linker comprising the amino acid sequence SGSETPGTSESATPES (SEQ ID NO: 7).


In some embodiments, the fusion protein comprises the amino acid residues 11-1629 of the amino acid sequence set forth in SEQ ID NO: 591. In some embodiments, the fusion protein comprises the amino acid sequence set forth in SEQ ID NO: 591. In some embodiments, the fusion protein comprises the amino acid sequence of any one of SEQ ID NOs: 5737, 5743, 5745, and 5746.


Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within a subject's genome, e.g., a human's genome. In some embodiments, fusion proteins of Cas9 (e.g., dCas9, nuclease active Cas9, or Cas9 nickase) and deaminases or deaminase domains, are provided. In some embodiments, methods for targeted nucleic acid editing are provided. In some embodiments, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of Cas9 and deaminases or deaminase domains, are provided.


Some aspects of this disclosure provide fusion proteins comprising a Cas9 protein as provided herein that is fused to a second protein (e.g., an enzymatic domain such as a cytidine deaminase domain), thus forming a fusion protein. In some embodiments, the second protein comprises an enzymatic domain, or a binding domain. In some embodiments, the enzymatic domain is a nuclease, a nickase, a recombinase, a deaminase, a methyltransferase, a methylase, an acetylase, an acetyltransferase, a transcriptional activator, or a transcriptional repressor domain. In some embodiments, the enzymatic domain is a nucleic acid editing domain. In some embodiments, the nucleic acid editing domain is a deaminase domain. In some embodiments, the deaminase is a cytosine deaminase or a cytidine deaminase. In some embodiments, the deaminase is an apolipoprotein B mRNA-editing complex (APOBEC) family deaminase. In some embodiments, the deaminase is an APOBEC1 deaminase. In some embodiments, the deaminase is an APOBEC2 deaminase. In some embodiments, the deaminase is an APOBEC3 deaminase. In some embodiments, the deaminase is an APOBEC3A deaminase. In some embodiments, the deaminase is an APOBEC3B deaminase. In some embodiments, the deaminase is an APOBEC3C deaminase. In some embodiments, the deaminase is an APOBEC3D deaminase. In some embodiments, the deaminase is an APOBEC3E deaminase. In some embodiments, the deaminase is an APOBEC3F deaminase. In some embodiments, the deaminase is an APOBEC3G deaminase. In some embodiments, the deaminase is an APOBEC3H deaminase. In some embodiments, the deaminase is an APOBEC4 deaminase. In some embodiments, the deaminase is an activation-induced deaminase (AID). It should be appreciated that the deaminase may be from any suitable organism (e.g., a human or a rat). In some embodiments, the deaminase is from a human, chimpanzee, gorilla, monkey, cow, dog, rat, or mouse. In some embodiments, the deaminase is rat APOBEC1 (SEQ ID NO: 284). In some embodiments, the deaminase is human APOBEC1 (SEQ ID NO: 282). In some embodiments, the deaminase is pmCDA1.


Some aspects of this disclosure provide fusion proteins comprising: (i) a nuclease-inactive Cas9 (dCas9) domain comprising the amino acid sequence of SEQ ID NO: 263; and (ii) an apolipoprotein B mRNA-editing complex 1 (APOBEC1) deaminase domain, wherein the deaminase domain is fused to the N-terminus of the dCas9 domain via a linker comprising the amino acid sequence of SGSETPGTSESATPES (SEQ ID NO: 7). In some embodiments, the deaminase is rat APOBEC1 (SEQ ID NO: 284). In some embodiments, the deaminase is human APOBEC1 (SEQ ID NO: 282). In some embodiments, the fusion protein comprises the amino acid sequence of SEQ ID NO: 591. In some embodiments, the fusion protein comprises the amino acid sequence of SEQ ID NO: 5737. In some embodiments, the deaminase is pmCDA1 (SEQ ID NO: 5738). In some embodiments, the deaminase is human APOBEC3G (SEQ ID NO: 275). In some embodiments, the deaminase is a human APOBEC3G variant of any one of SEQ ID NOs: 5739-5741.


Some aspects of this disclosure provide fusion proteins comprising: (i) a Cas9 nickase domain and (ii) an apolipoprotein B mRNA-editing complex 1 (APOBEC1) deaminase domain, wherein the deaminase domain is fused to the N-terminus of the Cas9 nickase domain. In some embodiments, the Cas9 nickase domain comprises a D10X mutation of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, wherein X is any amino acid except for D. In some embodiments, the amino acid sequence of the Cas9 nickase domain comprises a D10A mutation of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the amino acid sequence of the Cas9 nickase domain comprises a histidine at amino acid position 840 of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding amino acid position in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the amino acid sequence of the Cas9 nickase domain comprises the amino acid sequence as set forth in SEQ ID NO: 267. In some embodiments, the deaminase is rat APOBEC1 (SEQ ID NO: 284). In some embodiments, the deaminase is human APOBEC1 (SEQ ID NO: 282). In some embodiments, the deaminase is pmCDA1.


Some aspects of this disclosure provide fusion proteins comprising: (i) a Cas9 nickase domain and (ii) an apolipoprotein B mRNA-editing complex 1 (APOBEC1) deaminase domain, wherein the deaminase domain is fused to the N-terminus of the Cas9 nickase domain. In some embodiments, the Cas9 nickase domain comprises a D10× mutation of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, wherein X is any amino acid except for D. In some embodiments, the amino acid sequence of the Cas9 nickase domain comprises a D10A mutation of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the amino acid sequence of the Cas9 nickase domain comprises a histidine at amino acid position 840 of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding amino acid position in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the amino acid sequence of the Cas9 nickase domain comprises the amino acid sequence as set forth in SEQ ID NO: 267. In some embodiments, the deaminase is rat APOBEC1 (SEQ ID NO: 284). In some embodiments, the deaminase is human APOBEC1 (SEQ ID NO: 282). In some embodiments, the deaminase is pmCDAL.


Other aspects of this disclosure relate to the recognition that fusion proteins comprising a deaminase domain, a dCas9 domain and a uracil glycosylase inhibitor (UGI) domain demonstrate improved efficiency for deaminating target nucleotides in a nucleic acid molecule. Without wishing to be bound by any particular theory, cellular DNA-repair response to the presence of U:G heteroduplex DNA may be responsible for a decrease in nucleobase editing efficiency in cells. Uracil DNA glycosylase (UDG) catalyzes removal of U from DNA in cells, which may initiate base excision repair, with reversion of the U:G pair to a C:G pair as the most common outcome. As demonstrated herein, Uracil DNA Glycosylase Inhibitor (UGI) may inhibit human UDG activity. Without wishing to be bound by any particular theory, base excision repair may be inhibited by molecules that bind the single strand, block the edited base, inhibit UGI, inhibit base excision repair, protect the edited base, and/or promote “fixing” of the non-edited strand, etc.Thus, this disclosure contemplates fusion proteins comprising a dCas9-cytidine deaminase domain that is fused to a UGI domain.


In some embodiments, the fusion protein comprises a nuclease-inactive Cas9 (dCas9) domain; a nucleic acid editing domain; and a uracil glycosylase inhibitor (UGI) domain. In some embodiments, the dCas9 domain comprises a D10× mutation of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, wherein X is any amino acid except for D. In some embodiments, the amino acid sequence of the dCas9 domain comprises a D10A mutation of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the amino acid sequence of the dCas9 domain comprises an H840X mutation of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, wherein X is any amino acid except for H. In some embodiments, the amino acid sequence of the dCas9 domain comprises an H840A mutation of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the dCas9 domain comprises the amino acid sequence as set forth in SEQ ID NO: 263.


Further aspects of this disclosure relate to the recognition that fusion proteins using a Cas9 nickase as the Cas9 domain demonstrate improved efficiency for editing nucleic acids. For example, aspects of this disclosure relate to the recognition that fusion proteins comprising a Cas9 nickase, a deaminase domain and a UGI domain demonstrate improved efficiency for editing nucleic acids. For example, the improved efficiency for editing nucleotides is described below in the Examples section.


Some aspects of the disclosure are based on the recognition that any of the base editors provided herein are capable of modifying a specific nucleotide base without generating a significant proportion of indels. An “indel”, as used herein, refers to the insertion or deletion of a nucleotide base within a nucleic acid. Such insertions or deletions can lead to frame shift mutations within a coding region of a gene. In some embodiments, it is desirable to generate base editors that efficiently modify (e.g. mutate or deaminate) a specific nucleotide within a nucleic acid, without generating a large number of insertions or deletions (i.e., indels) in the nucleic acid. In certain embodiments, any of the base editors provided herein are capable of generating a greater proportion of intended modifications (e.g., point mutations or deaminations) versus indels.


Some aspects of the disclosure are based on the recognition that any of the base editors provided herein are capable of efficiently generating an intended mutation, such as a point mutation, in a nucleic acid (e.g. a nucleic acid within a genome of a subject) without generating a significant number of unintended mutations, such as unintended point mutations.


In some embodiments, a fusion protein comprises a Cas9 nickase domain, a nucleic acid editing domain; and a uracil glycosylase inhibitor (UGI) domain. In some embodiments, the amino acid sequence of the Cas9 nickase domain comprises a D10X mutation of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, wherein X is any amino acid except for D. In some embodiments, the amino acid sequence of the Cas9 nickase domain comprises a D10A mutation of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the amino acid sequence of the Cas9 nickase domain comprises a histidine at amino acid position 840 of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding amino acid position in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the amino acid sequence of the Cas9 nickase domain comprises the amino acid sequence as set forth in SEQ ID NO: 267.


In some embodiments, the deaminase domain of the fusion protein is fused to the N-terminus of the dCas9 domain or the Cas9 nickase. In some embodiments, the UGI domain is fused to the C-terminus of the dCas9 domain or the Cas9 nickase. In some embodiments, the dCas9 domain or the Cas9 nickase and the nucleic acid editing domain are fused via a linker. In some embodiments, the dCas9 domain or the Cas9 nickase and the UGI domain are fused via a linker.


In certain embodiments, linkers may be used to link any of the peptides or peptide domains of the invention. The linker may be as simple as a covalent bond, or it may be a polymeric linker many atoms in length. In certain embodiments, the linker is a polpeptide or based on amino acids. In other embodiments, the linker is not peptide-like. In certain embodiments, the linker is a covalent bond (e.g., a carbon-carbon bond, disulfide bond, carbon-heteroatom bond, etc.). In certain embodiments, the linker is a carbon-nitrogen bond of an amide linkage. In certain embodiments, the linker is a cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic or heteroaliphatic linker. In certain embodiments, the linker is polymeric (e.g., polyethylene, polyethylene glycol, polyamide, polyester, etc.). In certain embodiments, the linker comprises a monomer, dimer, or polymer of aminoalkanoic acid. In certain embodiments, the linker comprises an aminoalkanoic acid (e.g., glycine, ethanoic acid, alanine, beta-alanine, 3-aminopropanoic acid, 4-aminobutanoic acid, 5-pentanoic acid, etc.). In certain embodiments, the linker comprises a monomer, dimer, or polymer of aminohexanoic acid (Ahx). In certain embodiments, the linker is based on a carbocyclic moiety (e.g., cyclopentane, cyclohexane). In other embodiments, the linker comprises a polyethylene glycol moiety (PEG). In other embodiments, the linker comprises amino acids. In certain embodiments, the linker comprises a peptide. In certain embodiments, the linker comprises an aryl or heteroaryl moiety. In certain embodiments, the linker is based on a phenyl ring. The linker may included funtionalized moieties to facilitate attachment of a nucleophile (e.g., thiol, amino) from the peptide to the linker. Any electrophile may be used as part of the linker. Exemplary electrophiles include, but are not limited to, activated esters, activated amides, Michael acceptors, alkyl halides, aryl halides, acyl halides, and isothiocyanates.


In some embodiments, the linker comprises the amino acid sequence (GGGGS)n (SEQ ID NO: 5), (G)n, (EAAAK)n (SEQ ID NO: 6), (GGS)n, (SGGS), (SEQ ID NO: 4288), SGSETPGTSESATPES (SEQ ID NO: 7), (XP)n, or any combination thereof, wherein n is independently an integer between 1 and 30, and wherein X is any amino acid. In some embodiments, the linker comprises the amino acid sequence (GGS)n, wherein n is 1, 3, or 7. In some embodiments, the linker comprises the amino acid sequence SGSETPGTSESATPES (SEQ ID NO: 7).


In some embodiments, the fusion protein comprises the structure [nucleic acid editing domain]-[optional linker sequence]-[dCas9 or Cas9 nickase]-[optional linker sequence]-[UGI]. In some embodiments, the fusion protein comprises the structure [nucleic acid editing domain]-[optional linker sequence]-[UGI]-[optional linker sequence]-[dCas9 or Cas9 nickase]; [UGI]-[optional linker sequence]-[nucleic acid editing domain]-[optional linker sequence]-[dCas9 or Cas9 nickase]; [UGI]-[optional linker sequence]-[dCas9 or Cas9 nickase]-[optional linker sequence]-[nucleic acid editing domain]; [dCas9 or Cas9 nickase]-[optional linker sequence]-[UGI]-[optional linker sequence]-[nucleic acid editing domain]; or [dCas9 or Cas9 nickase]-[optional linker sequence]-[nucleic acid editing domain]-[optional linker sequence]-[UGI].


In some embodiments, the nucleic acid editing domain comprises a deaminase. In some embodiments, the nucleic acid editing domain comprises a deaminase. In some embodiments, the deaminase is a cytidine deaminase. In some embodiments, the deaminase is an apolipoprotein B mRNA-editing complex (APOBEC) family deaminase. In some embodiments, the deaminase is an APOBEC1 deaminase, an APOBEC2 deaminase, an APOBEC3A deaminase, an APOBEC3B deaminase, an APOBEC3C deaminase, an APOBEC3D deaminase, an APOBEC3F deaminase, an APOBEC3G deaminase, an APOBEC3H deaminase, or an APOBEC4 deaminase. In some embodiments, the deaminase is an activation-induced deaminase (AID). In some embodiments, the deaminase is a Lamprey CDA1 (pmCDA1) deaminase.


In some embodiments, the deaminase is from a human, chimpanzee, gorilla, monkey, cow, dog, rat, or mouse. In some embodiments, the deaminase is from a human. In some embodiments the deaminase is from a rat. In some embodiments, the deaminase is a rat APOBEC1 deaminase comprising the amino acid sequence set forth in (SEQ ID NO: 284). In some embodiments, the deaminase is a human APOBEC1 deaminase comprising the amino acid sequence set forth in (SEQ ID NO: 282). In some embodiments, the deaminase is pmCDA1 (SEQ ID NO: 5738). In some embodiments, the deaminase is human APOBEC3G (SEQ ID NO: 275). In some embodiments, the deaminase is a human APOBEC3G variant of any one of (SEQ ID NOs: 5739-5741). In some embodiments, the deaminase is at least 80%, at least 85%, at least 90%, at least 92%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to any one of the amino acid sequences set forth in SEQ ID NOs: 266-284 or 5725-5741.


In some embodiments, the UGI domain comprises an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 92%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to SEQ ID NO: 600. In some embodiments, the UGI domain comprises the amino acid sequence as set forth in SEQ ID NO: 600.


Some aspects of this disclosure provide complexes comprising a Cas9 protein or a Cas9 fusion protein as provided herein, and a guide RNA bound to the Cas9 protein or the Cas9 fusion protein.


Some aspects of this disclosure provide methods of using the Cas9 proteins, fusion proteins, or complexes provided herein. For example, some aspects of this disclosure provide methods comprising contacting a DNA molecule (a) with a Cas9 protein or a fusion protein as provided herein and with a guide RNA, wherein the guide RNA is about 15-100 nucleotides long and comprises a sequence of at least 10 contiguous nucleotides that is complementary to a target sequence; or (b) with a Cas9 protein, a Cas9 fusion protein, or a Cas9 protein or fusion protein complex with a gRNA as provided herein.


Some aspects of this disclosure provide kits comprising a nucleic acid construct, comprising (a) a nucleotide sequence encoding a Cas9 protein or a Cas9 fusion protein as provided herein; and (b) a heterologous promoter that drives expression of the sequence of (a). In some embodiments, the kit further comprises an expression construct encoding a guide RNA backbone, wherein the construct comprises a cloning site positioned to allow the cloning of a nucleic acid sequence identical or complementary to a target sequence into the guide RNA backbone.


Some aspects of this disclosure provide polynucleotides encoding a Cas9 protein of a fusion protein as provided herein. Some aspects of this disclosure provide vectors comprising such polynucleotides. In some embodiments, the vector comprises a heterologous promoter driving expression of polynucleotide.


Some aspects of this disclosure provide cells comprising a Cas9 protein, a fusion protein, a nucleic acid molecule, and/or a vector as provided herein.


The description of exemplary embodiments of the reporter systems above is provided for illustration purposes only and not meant to be limiting. Additional reporter systems, e.g., variations of the exemplary systems described in detail above, are also embraced by this disclosure.


The summary above is meant to illustrate, in a non-limiting manner, some of the embodiments, advantages, features, and uses of the technology disclosed herein. Other embodiments, advantages, features, and uses of the technology disclosed herein will be apparent from the Detailed Description, the Drawings, the Examples, and the Claims.





BRIEF DESCRIPTION OF THE DRAWINGS


FIG. 1 shows the deaminase activity of deaminases on single stranded DNA substrates. Single stranded DNA substrates using randomized PAM sequences (NNN PAM) were used as negative controls. Canonical PAM sequences used (NGG PAM)



FIG. 2 shows activity of Cas9:deaminase fusion proteins on single stranded DNA substrates.



FIG. 3 illustrates double stranded DNA substrate binding by Cas9:deaminase:sgRNA complexes.



FIG. 4 illustrates a double stranded DNA deamination assay.



FIG. 5 demonstrates that Cas9 fusions can target positions 3-11 of double-stranded DNA target sequences (numbered according to the schematic in FIG. 5). Upper Gel: 1 μM rAPOBEC1-GGS-dCas9, 125 nM dsDNA, 1 equivalent sgRNA. Mid Gel: 1 μM rAPOBEC1-(GGS)3(SEQ ID NO: 596)-dCas9, 125 nM dsDNA, 1 equivalent sgRNA. Lower Gel: 1.85 μM rAPOBEC1-XTEN-dCas9, 125 nM dsDNA, 1 equivalent sgRNA.



FIG. 6 demonstrates that the correct guide RNA, e.g., the correct sgRNA, is required for deaminase activity.



FIG. 7 illustrates the mechanism of target DNA binding of in vivo target sequences by deaminase-dCas9:sgRNA complexes.



FIG. 8 shows successful deamination of exemplary disease-associated target sequences.



FIG. 9 shows in vitro C→T editing efficiencies using His6-rAPOBEC1-XTEN-dCas9.



FIG. 10 shows C→T editing efficiencies in HEK293T cells is greatly enhanced by fusion with UGI.



FIGS. 11A to 11C show NBE1 mediates specific, guide RNA-programmed C to U conversion in vitro. FIG. 11A: Nucleobase editing strategy. DNA with a target C (red) at a locus specified by a guide RNA (green) is bound by dCas9 (blue), which mediates the local denaturation of the DNA substrate. Cytidine deamination by a tethered APOBEC1 enzyme (orange) converts the target C to U. The resulting G:U heteroduplex can be permanently converted to an A:T base pair following DNA replication or repair. If the U is in the template DNA strand, it will also result in an RNA transcript containing a G to A mutation following transcription. FIG. 11B: Deamination assay showing an activity window of approximately five nucleotides. Following incubation of NBE1-sgRNA complexes with dsDNA substrates at 37° C. for 2 h, the 5′ fluorophore-labeled DNA was isolated and incubated with USER enzyme (uracil DNA glycosylase and endonuclease VIII) at 37° C. for 1 h to induce DNA cleavage at the site of any uracils. The resulting DNA was resolved on a denaturing polyacrylamide gel, and any fluorophore-linked strands were visualized. Each lane is labeled according to the position of the target C within the protospacer, or with “—” if no target C is present, counting the base distal from the PAM as position 1. FIG. 11C: Deaminase assay showing the sequence specificity and sgRNA-dependence of NBE1. The DNA substrate with a target C at position 7 was incubated with NBE1 as in FIG. 11B with either the correct sgRNA, a mismatched sgRNA, or no sgRNA. No C to U editing is observed with the mismatched sgRNA or with no sgRNA. The positive control sample contains a DNA sequence with a U synthetically incorporated at position 7.



FIGS. 12A to 12B show effects of sequence context and target C position on nucleobase editing efficiency in vitro. FIG. 12A: Effect of changing the sequence surrounding the target C on editing efficiency in vitro. The deamination yield of 80% of targeted strands (40% of total sequencing reads from both strands) for C7 in the protospacer sequence 5′-TTATTTCGTGGATTTATTTA-3′(SEQ ID NO: 264) was defined as 1.0, and the relative deamination efficiencies of substrates containing all possible single-base mutations at positions 1-6 and 8-13 are shown. Values and error bars reflect the mean and standard deviation of two or more independent biological replicates performed on different days. FIG. 12B: Positional effect of each NC motif on editing efficiency in vitro. Each NC target motif was varied from positions 1 to 8 within the protospacer as indicated in the sequences shown on the right (the PAM shown in red, the protospacer plus one base 5′ to the protospacer are also shown). The percentage of total sequence reads containing T at each of the numbered target C positions following incubation with NBE1 is shown in the graph. Note that the maximum possible deamination yield in vitro is 50% of total sequencing reads (100% of targeted strands). Values and error bars reflect the mean and standard deviation of two or three independent biological replicates performed on different days. FIG. 12B depicts SEQ ID NOs: 285 through 292 from top to bottom, respectively.



FIGS. 13A to 13C show nucleobase editing in human cells. FIG. 13A: Protospacer (black) and PAM (red) sequences of the six mammalian cell genomic loci targeted by nucleobase editors. Target Cs are indicated with subscripted numbers corresponding to their positions within the protospacer. FIG. 13A depicts SEQ ID NOs: 293 through 298 from top to bottom, respectively. FIG. 13B: HEK293T cells were transfected with plasmids expressing NBE1, NBE2, or NBE3 and an appropriate sgRNA. Three days after transfection, genomic DNA was extracted and analyzed by high-throughput DNA sequencing at the six loci. Cellular C to T conversion percentages, defined as the percentage of total DNA sequencing reads with Ts at the target positions indicated, are shown for NBE1, NBE2, and NBE3 at all six genomic loci, and for wt Cas9 with a donor HDR template at three of the six sites (EMX1, HEK293 site 3, and HEK293 site 4). Values and error bars reflect the mean and standard deviation of three independent biological replicates performed on different days. FIG. 13C: Frequency of indel formation, calculated as described in the Methods, is shown following treatment of HEK293T cells with NBE2 and NBE3 for all six genomic loci, or with wt Cas9 and a single-stranded DNA template for HDR at three of the six sites (EMX1, HEK293 site 3, and HEK293 site 4). Values reflect the mean of at least three independent biological replicates performed on different days.



FIGS. 14A to 14C show NBE2- and NBE3-mediated correction of three disease-relevant mutations in mammalian cells. For each site, the sequence of the protospacer is indicated to the right of the name of the mutation, with the PAM highlighted in green and the base responsible for the mutation indicated in bold with a subscripted number corresponding to its position within the protospacer. The amino acid sequence above each disease-associated allele is shown, together with the corrected amino acid sequence following nucleobase editing in red. Underneath each sequence are the percentages of total sequencing reads with the corresponding base. Cells were nucleofected with plasmids encoding NBE2 or NBE3 and an appropriate sgRNA. Two days after nucleofection, genomic DNA was extracted and analyzed by HTS to assess pathogenic mutation correction. FIG. 14A: The Alzheimer's disease-associated APOE4 allele is converted to APOE3′ in mouse astrocytes by NBE3 in 11% of total reads (44% of nucleofected astrocytes). Two nearby Cs are also converted to Ts, but with no change to the predicted sequence of the resulting protein (SEQ ID NO: 299). FIG. 14B The cancer-associated p53 N239D mutation is corrected by NBE2 in 11% of treated human lymphoma cells (12% of nucleofected cells) that are heterozygous for the mutation (SEQ ID NO: 300). FIG. 14C The p53 Y163C mutation is corrected by NBE3 in 7.6% of nucleofected human breast cancer cells (SEQ ID NO: 301).



FIGS. 15A to 15D show effects of deaminase-dCas9 linker length and composition on nucleobase editing. Gel-based deaminase assay showing the deamination window of nucleobase editors with deaminase-Cas9 linkers of GGS (FIG. 15A), (GGS)3 (SEQ ID NO: 596) (FIG. 15B), XTEN (FIG. 15C), or (GGS)7 (SEQ ID NO: 597) (FIG. 15D). Following incubation of 1.85 μM editor-sgRNA complexes with 125 nM dsDNA substrates at 37° C. for 2 h, the dye-conjugated DNA was isolated and incubated with USER enzyme (uracil DNA glycosylase and endonuclease VIII) at 37° C. for an additional hour to cleave the DNA backbone at the site of any uracils. The resulting DNA was resolved on a denaturing polyacrylamide gel, and the dye-conjugated strand was imaged. Each lane is numbered according to the position of the target C within the protospacer, or with—if no target C is present. 8U is a positive control sequence with a U synthetically incorporated at position 8.



FIGS. 16A to 16B show NBE1 is capable of correcting disease-relevant mutations in vitro. FIG. 16A: Protospacer and PAM sequences (red) of seven disease-relevant mutations. The disease-associated target C in each case is indicated with a subscripted number reflecting its position within the protospacer. For all mutations except both APOE4 SNPs, the target C resides in the template (non-coding) strand. FIG. 16A depicts SEQ ID NOs: 302 through 308 from top to bottom, respectively. FIG. 16B: Deaminase assay showing each dsDNA oligonucleotide before (−) and after (+) incubation with NBE1, DNA isolation, and incubation with USER enzymes to cleave DNA at positions containing U. Positive control lanes from incubation of synthetic oligonucleotides containing U at various positions within the protospacer with USER enzymes are shown with the corresponding number indicating the position of the U.



FIG. 17 shows processivity of NBE1. The protospacer and PAM (red) of a 60-mer DNA oligonucleotide containing eight consecutive Cs is shown at the top. The oligonucleotide (125 nM) was incubated with NBE1 (2 μM) for 2 h at 37° C. The DNA was isolated and analyzed by high-throughput sequencing. Shown are the percent of total reads for the most frequent nine sequences observed. The vast majority of edited strands (>93%) have more than one C converted to T. This figure depicts SEQ ID NO: 309.



FIGS. 18A to 18H show the effect of fusing UGI to NBE1 to generate NBE2. FIG. 18A: Protospacer and PAM (red) sequences of the six mammalian cell genomic loci targeted with nucleobase editors. Editable Cs are indicated with labels corresponding to their positions within the protospacer. FIG. 18A depicts SEQ ID NOs: 293 through 298 from top to bottom, respectively. FIGS. 18B to 18G: HEK293T cells were transfected with plasmids expressing NBE1, NBE2, or NBE1 and UGI, and an appropriate sgRNA. Three days after transfection, genomic DNA was extracted and analyzed by high-throughput DNA sequencing at the six loci. Cellular C to T conversion percentages, defined as the percentage of total DNA sequencing reads with Ts at the target positions indicated, are shown for NBE1, NBE1 and UGI, and NBE2 at all six genomic loci. FIG. 18H: C to T mutation rates at 510 Cs surrounding the protospacers of interest for NBE1, NBE1 plus UGI on a separate plasmid, NBE2, and untreated cells are shown. The data show the results of 3,000,000 DNA sequencing reads from 1.5×106 cells. Values reflect the mean of at least two biological experiments conducted on different days.



FIG. 19 shows nucleobase editing efficiencies of NBE2 in U2OS and HEK293T cells. Cellular C to T conversion percentages by NBE2 are shown for each of the six targeted genomic loci in HEK293T cells and U2OS cells. HEK293T cells were transfected using lipofectamine 2000, and U2OS cells were nucleofected. U2OS nucleofection efficiency was 74%. Three days after plasmid delivery, genomic DNA was extracted and analyzed for nucleobase editing at the six genomic loci by HTS. Values and error bars reflect the mean and standard deviation of at least two biological experiments done on different days.



FIG. 20 shows nucleobase editing persists over multiple cell divisions. Cellular C to T conversion percentages by NBE2 are displayed at two genomic loci in HEK293T cells before and after passaging the cells. HEK293T cells were transfected using Lipofectamine 2000. Three days post transfection, the cells were harvested and split in half. One half was subjected to HTS analysis, and the other half was allowed to propagate for approximately five cell divisions, then harvested and subjected to HTS analysis.



FIG. 21 shows genetic variants from ClinVar that can be corrected in principle by nucleobase editing. The NCBI ClinVar database of human genetic variations and their corresponding phenotypes68 was searched for genetic diseases that can be corrected by current nucleobase editing technologies. The results were filtered by imposing the successive restrictions listed on the left. The x-axis shows the number of occurrences satisfying that restriction and all above restrictions on a logarithmic scale.



FIG. 22 shows in vitro identification of editable Cs in six genomic loci. Synthetic 80-mers with sequences matching six different genomic sites were incubated with NBE1 then analyzed for nucleobase editing via HTS. For each site, the sequence of the protospacer is indicated to the right of the name of the site, with the PAM highlighted in red. Underneath each sequence are the percentages of total DNA sequencing reads with the corresponding base. A target C was considered as “editable” if the in vitro conversion efficiency is >10%. Note that maximum yields are 50% of total DNA sequencing reads since the non-targeted strand is not a substrate for nucleobase editing. This figure depicts SEQ ID NOs: 293 through 298 from top to bottom, respectively.



FIG. 23 shows activities of NBE1, NBE2, and NBE3 at EMX1 off-targets. HEK293T cells were transfected with plasmids expressing NBE1, NBE2, or NBE3 and a sgRNA matching the EMX1 sequence using Lipofectamine 2000. Three days after transfection, genomic DNA was extracted, amplified by PCR, and analyzed by high-throughput DNA sequencing at the on-target loci, plus the top ten known Cas9 off-target loci for the EMX1 sgRNA, as previously determined using the GUIDE-seq method55. EMX1 off-target 5 locus did not amplify and is not shown. Sequences of the on-target and off-target protospacers and protospacer adjacent motifs (PAMs) are displayed. Cellular C to T conversion percentages, defined as the percentage of total DNA sequencing reads with T at each position of an original C within the protospacer, are shown for NBE1, NBE2, and NBE3. On the far right are displayed the total number of sequencing reads reported for each sequence. This figure depicts SEQ ID NOs: 293, and 310 through 318 from top to bottom, respectively.



FIG. 24 shows activities of NBE1, NBE2, and NBE3 at FANCF off-targets. HEK293T cells were transfected with plasmids expressing NBE1, NBE2, or NBE3 and a sgRNA matching the FANCF sequence using Lipofectamine 2000. Three days after transfection, genomic DNA was extracted, amplified by PCR, and analyzed by high-throughput DNA sequencing at the on-target loci, plus all of the known Cas9 off-target loci for the FANCF sgRNA, as previously determined using the GUIDE-seq method55. Sequences of the on-target and off-target protospacers and protospacer adjacent motifs (PAMs) are displayed. Cellular C to T conversion percentages, defined as the percentage of total DNA sequencing reads with T at each position of an original C within the protospacer, are shown for NBE1, NBE2, and NBE3. On the far right are displayed the total number of sequencing reads reported for each sequence. This figure depicts SEQ ID NOs: 294 and 319 through 326 from top to bottom, respectively.



FIG. 25 shows activities of NBE1, NBE2, and NBE3 at HEK293 site 2 off-targets. HEK293T cells were transfected with plasmids expressing NBE1, NBE2, or NBE3 and a sgRNA matching the HEK293 site 2 sequence using Lipofectamine 2000. Three days after transfection, genomic DNA was extracted, amplified by PCR, and analyzed by high-throughput DNA sequencing at the on-target loci, plus all of the known Cas9 off-target loci for the HEK293 site 2 sgRNA, as previously determined using the GUIDE-seq method55. Sequences of the on-target and off-target protospacers and protospacer adjacent motifs (PAMs) are displayed. Cellular C to T conversion percentages, defined as the percentage of total DNA sequencing reads with T at each position of an original C within the protospacer, are shown for NBE1, NBE2, and NBE3. On the far right are displayed the total number of sequencing reads reported for each sequence. This figure depicts SEQ ID NOs: 295, 327, and 328 from top to bottom, respectively.



FIG. 26 shows activities of NBE1, NBE2, and NBE3 at HEK293 site 3 off-targets. HEK293T cells were transfected with plasmids expressing NBE1, NBE2, or NBE3 and a sgRNA matching the HEK293 site 3 sequence using Lipofectamine 2000. Three days after transfection, genomic DNA was extracted, amplified by PCR, and analyzed by high-throughput DNA sequencing at the on-target loci, plus all of the known Cas9 off-target loci for the HEK293 site 3 sgRNA, as previously determined using the GUIDE-seq method55. Sequences of the on-target and off-target protospacers and protospacer adjacent motifs (PAMs) are displayed. Cellular C to T conversion percentages, defined as the percentage of total DNA sequencing reads with T at each position of an original C within the protospacer, are shown for NBE1, NBE2, and NBE3. On the far right are displayed the total number of sequencing reads reported for each sequence. This figure depicts SEQ ID NOs: 296 and 659 through 663 from top to bottom, respectively.



FIG. 27 shows activities of NBE1, NBE2, and NBE3 at HEK293 site 4 off-targets. HEK293T cells were transfected with plasmids expressing NBE1, NBE2, or NBE3 and a sgRNA matching the HEK293 site 4 sequence using Lipofectamine 2000. Three days after transfection, genomic DNA was extracted, amplified by PCR, and analyzed by high-throughput DNA sequencing at the on-target loci, plus the top ten known Cas9 off-target loci for the HEK293 site 4 sgRNA, as previously determined using the GUIDE-seq method55. Sequences of the on-target and off-target protospacers and protospacer adjacent motifs (PAMs) are displayed. Cellular C to T conversion percentages, defined as the percentage of total DNA sequencing reads with T at each position of an original C within the protospacer, are shown for NBE1, NBE2, and NBE3. On the far right are displayed the total number of sequencing reads reported for each sequence. This figure depicts SEQ ID NOs: 297 and 664 through 673 from top to bottom, respectively.



FIG. 28 shows non-target C mutation rates. Shown here are the C to T mutation rates at 2,500 distinct cytosines surrounding the six on-target and 34 off-target loci tested, representing a total of 14,700,000 sequence reads derived from approximately 1.8×106 cells.



FIGS. 29A to 29C show base editing in human cells. FIG. 29A shows possible base editing outcomes in mammalian cells. Initial editing resulted in a U:G mismatch. Recognition and excision of the U by uracil DNA glycosylase (UDG) initiated base excision repair (BER), which lead to reversion to the C:G starting state. BER was impeded by BE2 and BE3, which inhibited UDG. The U:G mismatch was also processed by mismatch repair (MMR), which preferentially repaired the nicked strand of a mismatch. BE3 nicked the non-edited strand containing the G, favoring resolution of the U:G mismatch to the desired U:A or T:A outcome. FIG. 29B shows HEK293T cells treated as described in the Materials and Methods in the Examples below. The percentage of total DNA sequencing read with Ts at the target positions indicated show treatment with BE1, BE2, or BE3, or for treatment with wt Cas9 with a donor HDR template. FIG. 29C shows frequency of indel formation following the treatment in FIG. 29B. Values are listed in FIG. 34. For FIGS. 29B and 29C, values and error bars reflect the mean and s.d. of three independent biological replicates performed on different days.



FIGS. 30A to 30B show BE3-mediated correction of two disease-relevant mutations in mammalian cells. The sequence of the protospacer is shown to the right of the mutation, with the PAM in blue and the target base in red with a subscripted number indicating its position within the protospacer. Underneath each sequence are the percentages of total sequencing reads with the corresponding base. Cells were treated as described in the Materials and Methods. FIG. 30A shows the Alzheimer's disease-associated APOE4 allele converted to APOE3r in mouse astrocytes by BE3 in 74.9% of total reads. Two nearby Cs were also converted to Ts, but with no change to the predicted sequence of the resulting protein. Identical treatment of these cells with wt Cas9 and donor ssDNA results in only 0.3% correction, with 26.1% indel formation. FIG. 30B shows the cancer associated p53 Y163C mutation corrected by BE3 in 7.6% of nucleofected human breast cancer cells with 0.7% indel formation. Identical treatment of these cells with wt Cas9 and donor ssDNA results in no mutation correction with 6.1% indel formation. This figure depicts SEQ ID NOs: 675 to 680 from top to bottom, respectively.



FIG. 31 shows activities of BE1, BE2, and BE3 at HEK293 site 2 off-targets. HEK293T cells were transfected with plasmids expressing BE1, BE2, or BE3 and a sgRNA matching the HEK293 site 2 sequence using Lipofectamine 2000. Three days after transfection, genomic DNA was extracted, amplified by PCR, and analyzed by high-throughput DNA sequencing at the on-target loci, plus all of the known Cas9 and dCas9 off-target loci for the HEK293 site 2 sgRNA, as previously determined by Joung and coworkers using the GUIDE-seq method (63), and Adli and coworkers using chromatin immunoprecipitation high-throughput sequencing (ChIP-seq) experiments (18). Sequences of the on-target and off-target protospacers and protospacer adjacent motifs (PAMs) are displayed. Cellular C to T conversion percentages, defined as the percentage of total DNA sequencing reads with T at each position of an original C within the protospacer, are shown for BE1, BE2, and BE3. On the far right are displayed the total number of sequencing reads reported, and the ChIP-seq signal intensity reported for each sequence. This figure depicts SEQ ID NOs: 681 to 688 from top to bottom, respectively.



FIG. 32 shows activities of BE1, BE2, and BE3 at HEK293 site 3 off-targets. HEK293T cells were transfected with plasmids expressing BE1, BE2, or BE3 and a sgRNA matching the HEK293 site 3 sequence using Lipofectamine 2000. Three days after transfection, genomic DNA was extracted, amplified by PCR, and analyzed by high-throughput DNA sequencing at the on-target loci, plus all of the known Cas9 off-target loci and the top five known dCas9 off-target loci for the HEK293 site 3 sgRNA, as previously determined by Joung and coworkers using the GUIDE-seq method54, and using chromatin immunoprecipitation high-throughput sequencing (ChIP-seq) experiments61. Sequences of the on-target and off-target protospacers and protospacer adjacent motifs (PAMs) are displayed. Cellular C to T conversion percentages, defined as the percentage of total DNA sequencing reads with T at each position of an original C within the protospacer, are shown for BE1, BE2, and BE3. On the far right are displayed the total number of sequencing reads reported, and the ChIP-seq signal intensity reported for each sequence. This figure depicts SEQ ID NOs: 689 to 699 from top to bottom, respectively.



FIG. 33 shows activities of BE1, BE2, and BE3 at HEK293 site 4 off-targets. HEK293T cells were transfected with plasmids expressing BE1, BE2, or BE3 and a sgRNA matching the HEK293 site 4 sequence using Lipofectamine 2000. Three days after transfection, genomic DNA was extracted, amplified by PCR, and analyzed by high-throughput DNA sequencing at the on-target loci, plus the top ten known Cas9 off-target loci and the top five known dCas9 off-target loci for the HEK293 site 4 sgRNA, as previously determined using the GUIDE-seq method54, and using chromatin immunoprecipitation high-throughput sequencing (ChIP-seq) experiments61. Sequences of the on-target and off-target protospacers and protospacer adjacent motifs (PAMs) are displayed. Cellular C to T conversion percentages, defined as the percentage of total DNA sequencing reads with T at each position of an original C within the protospacer, are shown for BE1, BE2, and BE3. On the far right are displayed the total number of sequencing reads reported, and the ChIP-seq signal intensity reported for each sequence. This figure depicts SEQ ID NOs: 700 to 712 from top to bottom, respectively.



FIG. 34 shows mutation rates of non-protospacer bases following BE3-mediated correction of the Alzheimer's disease-associated APOE4 allele to APOE3r in mouse astrocytes. The DNA sequence of the 50 bases on either side of the protospacer from FIG. 30A and FIG. 34B is shown with each base's position relative to the protospacer. The side of the protospacer distal to the PAM is designated with positive numbers, while the side that includes the PAM is designated with negative numbers, with the PAM shown in blue. Underneath each sequence are the percentages of total DNA sequencing reads with the corresponding base for untreated cells, for cells treated with BE3 and an sgRNA targeting the APOE4 C158R mutation, or for cells treated with BE3 and an sgRNA targeting the VEGFA locus. Neither BE3-treated sample resulted in mutation rates above those of untreated controls. This figure depicts SEQ ID NOs: 713 to 716 from top to bottom, respectively.



FIG. 35 shows mutation rates of non-protospacer bases following BE3-mediated correction of the cancer-associated p53 Y163C mutation in HCC1954 human cells. The DNA sequence of the 50 bases on either side of the protospacer from FIG. 30B and FIG. 39B is shown with each base's position relative to the protospacer. The side of the protospacer distal to the PAM is designated with positive numbers, while the side that includes the PAM is designated with negative numbers, with the PAM shown in blue. Underneath each sequence are the percentages of total sequencing reads with the corresponding base for untreated cells, for cells treated with BE3 and an sgRNA targeting the TP53 Y163C mutation, or for cells treated with BE3 and an sgRNA targeting the VEGFA locus. Neither BE3-treated sample resulted in mutational rates above those of untreated controls. This figure depicts SEQ ID NOs: 717 to 720 from top to bottom, respectively.



FIGS. 36A to 36F show the effects of deaminase, linker length, and linker composition on base editing. FIG. 36A shows a gel-based deaminase assay showing activity of rAPOBEC1, pmCDA1, hAID, hAPOBEC3G, rAPOBEC1-GGS-dCas9, rAPOBEC1-(GGS)3(SEQ ID NO: 596)-dCas9, and dCas9-(GGS)3(SEQ ID NO: 596)-rAPOBEC1 on ssDNA. Enzymes were expressed in a mammalian cell lysate-derived in vitro transcription-translation system and incubated with 1.8 μM dye-conjugated ssDNA and USER enzyme (uracil DNA glycosylase and endonuclease VIII) at 37° C. for 2 hours. The resulting DNA was resolved on a denaturing polyacrylamide gel and imaged. The positive control is a sequence with a U synthetically incorporated at the same position as the target C. FIG. 36B shows coomassie-stained denaturing PAGE gel of the expressed and purified proteins used in FIGS. 36C to 36F. FIGS. 36C to 36F show gel-based deaminase assay showing the deamination window of base editors with deaminase-Cas9 linkers of GGS (FIG. 36C), (GGS)3 (SEQ ID NO: 596) (FIG. 36D), XTEN (FIG. 36E), or (GGS)7 (SEQ ID NO: 597) (FIG. 36F). Following incubation of 1.85 μM deaminase-dCas9 fusions complexed with sgRNA with 125 nM dsDNA substrates at 37° C. for 2 hours, the dye-conjugated DNA was isolated and incubated with USER enzyme at 37° C. for 1 hour to cleave the DNA backbone at the site of any uracils. The resulting DNA was resolved on a denaturing polyacrylamide gel, and the dye-conjugated strand was imaged. Each lane is numbered according to the position of the target C within the protospacer, or with—if no target C is present. 8U is a positive control sequence with a U synthetically incorporated at position 8.



FIGS. 37A to 37C show BE1 base editing efficiencies are dramatically decreased in mammalian cells. FIG. 37A Protospacer (black and red) and PAM (blue) sequences of the six mammalian cell genomic loci targeted by base editors. Target Cs are indicated in red with subscripted numbers corresponding to their positions within the protospacer. FIG. 37B shows synthetic 80-mers with sequences matching six different genomic sites were incubated with BE1 then analyzed for base editing by HTS. For each site, the sequence of the protospacer is indicated to the right of the name of the site, with the PAM highlighted in blue. Underneath each sequence are the percentages of total DNA sequencing reads with the corresponding base. We considered a target C as “editable” if the in vitro conversion efficiency is >10%. Note that maximum yields are 50% of total DNA sequencing reads since the non-targeted strand is unaffected by BE1. Values are shown from a single experiment. FIG. 37C shows HEK293T cells were transfected with plasmids expressing BE1 and an appropriate sgRNA. Three days after transfection, genomic DNA was extracted and analyzed by high-throughput DNA sequencing at the six loci. Cellular C to T conversion percentages, defined as the percentage of total DNA sequencing reads with Ts at the target positions indicated, are shown for BE1 at all six genomic loci. Values and error bars of all data from HEK293T cells reflect the mean and standard deviation of three independent biological replicates performed on different days. FIG. 37A depicts SEQ ID NOs: 721 to 726 from top to bottom, respectively. FIG. 37B depicts SEQ ID NOs: 727 to 732 from top to bottom, respectively.



FIG. 38 shows base editing persists over multiple cell divisions. Cellular C to T conversion percentages by BE2 and BE3 are shown for HEK293 sites 3 and 4 in HEK293T cells before and after passaging the cells. HEK293T cells were nucleofected with plasmids expressing BE2 or BE3 and an sgRNA targeting HEK293 site 3 or 4. Three days after nucleofection, the cells were harvested and split in half. One half was subjected to HTS analysis, and the other half was allowed to propagate for approximately five cell divisions, then harvested and subjected to HTS analysis. Values and error bars reflect the mean and standard deviation of at least two biological experiments.



FIGS. 39A to 39C show non-target C/G mutation rates. Shown here are the C to T and G to A mutation rates at 2,500 distinct cytosines and guanines surrounding the six on-target and 34 off-target loci tested, representing a total of 14,700,000 sequence reads derived from approximately 1.8×106 cells. FIGS. 39A and 39B show cellular non-target C to T and G to A conversion percentages by BE1, BE2, and BE3 are plotted individually against their positions relative to a protospacer for all 2,500 cytosines/guanines. The side of the protospacer distal to the PAM is designated with positive numbers, while the side that includes the PAM is designated with negative numbers. FIG. 39C shows average non-target cellular C to T and G to A conversion percentages by BE1, BE2, and BE3 are shown, as well as the highest and lowest individual conversion percentages.



FIGS. 40A to 40B show additional data sets of BE3-mediated correction of two disease-relevant mutations in mammalian cells. For each site, the sequence of the protospacer is indicated to the right of the name of the mutation, with the PAM highlighted in blue and the base responsible for the mutation indicated in red bold with a subscripted number corresponding to its position within the protospacer. The amino acid sequence above each disease-associated allele is shown, together with the corrected amino acid sequence following base editing in green. Underneath each sequence are the percentages of total sequencing reads with the corresponding base. Cells were nucleofected with plasmids encoding BE3 and an appropriate sgRNA. Two days after nucleofection, genomic DNA was extracted from the nucleofected cells and analyzed by HTS to assess pathogenic mutation correction. FIG. 40A shows the Alzheimer's disease-associated APOE4 allele is converted to APOE3r in mouse astrocytes by BE3 in 58.3% of total reads only when treated with the correct sgRNA. Two nearby Cs are also converted to Ts, but with no change to the predicted sequence of the resulting protein. Identical treatment of these cells with wt Cas9 and donor ssDNA results in 0.2% correction, with 26.7% indel formation. FIG. 40B shows the cancer-associated p53 Y163C mutation is corrected by BE3 in 3.3% of nucleofected human breast cancer cells only when treated with the correct sgRNA. Identical treatment of these cells with wt Cas9 and donor ssDNA results in no detectable mutation correction with 8.0% indel formation. FIGS. 40A to 40B depict SEQ ID NOs: 733 to 740 from top to bottom, respectively.



FIG. 41 shows a schematic representation of an exemplary USER (Uracil-Specific Excision Reagent) Enzyme-based assay, which may be used to test the activity of various deaminases on single-stranded DNA (ssDNA) substrates.



FIG. 42 is a schematic of the pmCDA-nCas9-UGI-NLS construct and its activity at the HeK-3 site relative to the base editor (rAPOBEC1) and the negative control (untreated).



FIG. 43 is a schematic of the pmCDA1-XTEN-nCas9-UGI-NLS construct and its activity at the HeK-3 site relative to the base editor (rAPOBEC1) and the negative control (untreated).



FIG. 44 shows the percent of total sequencing reads with target C converted to T using cytidine deaminases (CDA) or APOBEC.



FIG. 45 shows the percent of total sequencing reads with target C converted to A using deaminases (CDA) or APOBEC.



FIG. 46 shows the percent of total sequencing reads with target C converted to G using deaminases (CDA) or APOBEC.



FIG. 47 is a schematic of the huAPOBEC3G-XTEN-nCas9-UGI-NLS construct and its activity at the HeK-2 site relative to a mutated form (huAPOBEC3G*(D316R_D317R)-XTEN-nCas9-UGI-NLS, the base editor (rAPOBEC1) and the negative control (untreated).



FIG. 48 shows the schematic of the LacZ construct used in the selection assay of Example 7.



FIG. 49 shows reversion data from different plasmids and constructs.



FIG. 50 shows the verification of lacZ reversion and the purification of reverted clones.



FIG. 51 is a schematic depicting a deamination selection plasmid used in Example 7.



FIG. 52 shows the results of a chloramphenicol reversion assay (pmCDA1 fusion).



FIGS. 53A to 53B demonstrated DNA correction induction of two constructs.



FIG. 54 shows the results of a chloramphenicol reversion assay (huAPOBEC3G fusion).



FIG. 55 shows the activities of BE3 and HF-BE3 at EMX1 off-targets. The sequences, from top to bottom, correspond to SEQ ID NOs: 286-292, 299-301.



FIG. 56 shows on-target base editing efficiencies of BE3 and HF-BE3.



FIG. 57 is a graph demonstrating that mutations affect cytidine deamination with varying degrees. Combinations of mutations that each slightly impairs catalysis allow selective deamination at one position over others. The FANCF site was GGAATC6C7C8TTC11TGCAGCACCTGG (SEQ ID NO: 303).



FIG. 58 is a schematic depicting next generation base editors.



FIG. 59 is a schematic illustrating new base editors made from Cas9 variants.



FIG. 60 shows the base-edited percentage of different NGA PAM sites.



FIG. 61 shows the base-edited percentage of cytidines using NGCG PAM EMX (VRER BE3) and the C1TC3C4C5ATC8AC10ATCAACCGGT (SEQ ID NO: 304) spacer.



FIG. 62 shows the based-edited percentages resulting from different NNGRRT PAM sites.



FIG. 63 shows the based-edited percentages resulting from different NNHRRT PAM sites.



FIGS. 64A to 64C show the base-edited percentages resulting from different TTTN PAM sites using Cpf1 BE2. The spacers used were: TTTCCTC3C4C5C6C7C8C9AC10iAGGTAGAACAT (FIG. 64A, SEQ ID NO: 305), TTTCC1C2TC4TGTC8C9AC11ACCCTCATCCTG (FIG. 64B, SEQ ID NO: 306), and TTTCC1C2C3AGTC7C8TC10C11AC13AC15C16C17TGAAAC (FIG. 64C, SEQ ID NO: 307).



FIG. 65 is a schematic depicting selective deamination as achieved through kinetic modulation of cytidine deaminase point mutagenesis.



FIG. 66 is a graph showing the effect of various mutations on the deamination window probed in cell culture with multiple cytidines in the spacer. The spacer used was: TGC3C4C5C6TC8C9C10TC12C13C14TGGCCC (SEQ ID NO: 308).



FIG. 67 is a graph showing the effect of various mutations on the deamination window probed in cell culture with multiple cytidines in the spacer. The spacer used was: AGAGC5C6C7C8C9C10C11TC13AAAGAGA (SEQ ID NO: 309).



FIG. 68 is a graph showing the effect of various mutations on the FANCF site with a limited number of cytidines. The spacer used was: GGAATC6C7C8TTC11TGCAGCACCTGG (SEQ ID NO: 303). Note that the triple mutant (W90Y, R126E, R132E) preferentially edits the cytidine at the sixth position.



FIG. 69 is a graph showing the effect of various mutations on the HEK3 site with a limited number of cytidines. The spacer used was: GGCC4C5AGACTGAGCACGTGATGG (SEQ ID NO: 310). Note that the double and triple mutants preferentially edit the cytidine at the fifth position over the cytidine in the fourth position.



FIG. 70 is a graph showing the effect of various mutations on the EMX1 site with a limited number of cytidines. The spacer used was: GAGTC5C6GAGCAGAAGAAGAAGGG (SEQ ID NO: 311). Note that the triple mutant only edits the cytidine at the fifth position, not the sixth.



FIG. 71 is a graph showing the effect of various mutations on the HEK2 site with a limited number of cytidines. The spacer used was: GAAC4AC6AAAGCATAGACTGCGGG (SEQ ID NO: 312).



FIG. 72 shows on-target base editing efficiencies of BE3 and BE3 comprising mutations W90Y R132E in immortalized astrocytes.



FIG. 73 depicts a schematic of three Cpf1 fusion constructs.



FIG. 74 shows a comparison of plasmid delivery of BE3 and HF-BE3 (EMX1, FANCF, and RNF2).



FIG. 75 shows a comparison of plasmid delivery of BE3 and HF-BE3 (HEK3 and HEK 4).



FIG. 76 shows off-target editing of EMX-1 at all 10 sites.



FIG. 77 shows deaminase protein lipofection to HEK cells using a GAGTCCGAGCAGAAGAAGAAG (SEQ ID NO: 313) spacer. The EMX-1 on-target and EMX-1 off target site 2 were examined.



FIG. 78 shows deaminase protein lipofection to HEK cells using a GGAATCCCTTCTGCAGCACCTGG (SEQ ID NO: 314) spacer. The FANCF on target and FANCF off target site 1 were examined.



FIG. 79 shows deaminase protein lipofection to HEK cells using a GGCCCAGACTGAGCACGTGA (SEQ ID NO: 315) spacer. The HEK-3 on target site was examined.



FIG. 80 shows deaminase protein lipofection to HEK cells using a GGCACTGCGGCTGGAGGTGGGGG (SEQ ID NO: 316) spacer. The HEK-4 on target, off target site 1, site 3, and site 4.



FIG. 81 shows the results of an in vitro assay for sgRNA activity for sgHR_13 (GTCAGGTCGAGGGTTCTGTC (SEQ ID NO: 317) spacer; C8 target: G51 to STOP), sgHR_14 (GGGCCGCAGTATCCTCACTC (SEQ ID NO: 318) spacer; C7 target; C7 target: Q68 to STOP), and sgHR_15 (CCGCCAGTCCCAGTACGGGA (SEQ ID NO: 319) spacer; C10 and C11 are targets: W239 or W237 to STOP).



FIG. 82 shows the results of an in vitro assay for sgHR_17 (CAACCACTGCTCAAAGATGC (SEQ ID NO: 320) spacer; C4 and C5 are targets: W410 to STOP), and sgHR_16 (CTTCCAGGATGAGAACACAG (SEQ ID NO: 321) spacer; C4 and C5 are targets: W273 to STOP).



FIG. 83 shows the direct injection of BE3 protein complexed with sgHR_13 in zebrafish embryos.



FIG. 84 shows the direct injection of BE3 protein complexed with sgHR_16 in zebrafish embryos.



FIG. 85 shows the direct injection of BE3 protein complexed with sgHR_17 in zebrafish embryos.



FIG. 86 shows exemplary nucleic acid changes that may be made using base editors that are capable of making a cytosine to thymine change.



FIG. 87 shows an illustration of apolipoprotein E (APOE) isoforms, demonstrating how a base editor (e.g., BE3) may be used to edit one APOE isoform (e.g., APOE4) into another APOE isoform (e.g., APOE3r) that is associated with a decreased risk of Alzheimer's disease.



FIG. 88 shows base editing of APOE4 to APOE3r in mouse astrocytes.



FIG. 89 shows base editing of PRNP to cause early truncation of the protein at arginine residue 37.



FIG. 90 shows that knocking out UDG (which UGI inhibits) dramatically improves the cleanliness of efficiency of C to T base editing.



FIG. 91 shows that use of a base editor with the nickase but without UGI leads to a mixture of outcomes, with very high indel rates.



FIGS. 92A to 92G show that SaBE3, SaKKH-BE3, VQR-BE3, EQR-BE3, and VRER-BE3 mediate efficient base editing at target sites containing non-NGG PAMs in human cells. FIG. 92A shows base editor architectures using S. pyogenes and S. aureus Cas9. FIG. 92B shows recently characterized Cas9 variants with alternate or relaxed PAM requirements. FIGS. 92C and 92D show HEK293T cells treated with the base editor variants shown as described in Example 12. The percentage of total DNA sequencing reads (with no enrichment for transfected cells) with C converted to T at the target positions indicated are shown. The PAM sequence of each target tested is shown below the X-axis. The charts show the results for SaBE3 and SaKKH-BE3 at genomic loci with NNGRRT PAMs (FIG. 92C), SaBE3 and SaKKH-BE3 at genomic loci with NNNRRT PAMs (FIG. 92D), VQR-BE3 and EQR-BE3 at genomic loci with NGAG PAMs (FIG. 92E), and with NGAH PAMs (FIG. 92F), and VRER-BE3 at genomic loci with NGCG PAMs (FIG. 92G). Values and error bars reflect the mean and standard deviation of at least two biological replicates.



FIGS. 93A to 93C demonstrate that base editors with mutations in the cytidine deaminase domain exhibit narrowed editing windows. FIGS. 93A to 93C show HEK293T cells transfected with plasmids expressing mutant base editors and an appropriate sgRNA. Three days after transfection, genomic DNA was extracted and analyzed by high-throughput DNA sequencing at the indicated loci. The percentage of total DNA sequencing reads (without enrichment for transfected cells) with C changed to T at the target positions indicated are shown for the EMX1 site, HEK293 site 3, FANCF site, HEK293 site 2, site A, and site B loci. FIG. 93A illustrates certain cytidine deaminase mutations which narrow the base editing window. See FIG. 98 for the characterization of additional mutations. FIG. 93B shows the effect of cytidine deaminase mutations which effect the editing window width on genomic loci. Combining beneficial mutations has an additive effect on narrowing the editing window. FIG. 93C shows that YE1-BE3, YE2-BE3, EE-BE3, and YEE-BE3 effect the product distribution of base editing, producing predominantly singly-modified products in contrast with BE3. Values and error bars reflect the mean and standard deviation of at least two biological replicates.



FIGS. 94A and 94B show genetic variants from ClinVar that in principle can be corrected by the base editors developed in this work. The NCBI ClinVar database of human genetic variations and their corresponding phenotypes was searched for genetic diseases that in theory can be corrected by base editing. FIG. 94A demonstrates improvement in base editing targeting scope among all pathogenic T→C mutations in the ClinVar database through the use of base editors with altered PAM specificities. The white fractions denote the proportion of pathogenic T→C mutations accessible on the basis of the PAM requirements of either BE3, or BE3 together with the five modified-PAM base editors developed in this work. FIG. 94B shows improvement in base editing targeting scope among all pathogenic T→C mutations in the ClinVar database through the use of base editors with narrowed activity windows. BE3 was assumed to edit Cs in positions 4-8 with comparable efficiency as shown in FIGS. 93A to 93C. YEE-BE3 was assumed to edit with C5>C6>C7>others preference within its activity window. The white fractions denote the proportion of pathogenic T→C mutations that can be edited BE3 without comparable editing of other Cs (left), or that can be edited BE3 or YEE-BE3 without comparable editing of other Cs (right).



FIGS. 95A and 95B show the effect of truncated guide RNAs on base editing window width. HEK293T cells were transfected with plasmids expressing BE3 and sgRNAs of different 5′ truncation lengths. The treated cells were analyzed as described in the Examples. FIG. 95A shows protospacer and PAM sequence (top, SEQ ID NO: 4270) and cellular C to T conversion percentages, defined as the percentage of total DNA sequencing reads with Ts at the target positions indicated, at a site within the EMX1 genomic locus. At this site, the base editing window was altered through the use of a 17-nt truncated gRNA. FIG. 95B shows protospacer and PAM sequences (top, SEQ ID NO: 4270) and cellular C to T conversion percentages, defined as the percentage of total DNA sequencing reads with Ts at the target positions indicated, at sites within the HEK site 3 and site 4 genomic loci. At these sites, no change in the base editing window was observed, but a linear decrease in editing efficiency for all substrate bases as the sgRNA is truncated was noted.



FIG. 96 shows the effect of APOBEC1-Cas9 linker lengths on base editing window width. HEK293T cells were transfected with plasmids expressing base editors with rAPOBEC1-Cas9 linkers of XTEN, GGS, (GGS)3 (SEQ ID NO: 596), (GGS)5(SEQ ID NO: 4271), or (GGS)7 (SEQ ID NO: 597) and an sgRNA. The treated cells were analyzed as described in the Examples. Cellular C to T conversion percentages, defined as the percentage of total DNA sequencing reads with Ts at the target positions indicated, are shown for the various base editors with different linkers.



FIGS. 97A to 97C show the effect of rAPOBEC mutations on base editing window width. FIG. 97C shows HEK293T cells transfected with plasmids expressing an sgRNA targeting either Site A or Site B and the BE3 point mutants indicated. The treated cells were analyzed as described in the Examples. All C's in the protospacer and within three basepairs of the protospacer are displayed and the cellular C to T conversion percentages are shown. The ‘editing window widths’, defined as the calculated number of nucleotides within which editing efficiency exceeds the half-maximal value, are displayed for all tested mutants.



FIG. 98 shows the effect of APOBEC1 mutation son product distributions of base editing in mammalian cells. HEK293T cells were transfected with plasmids expressing BE3 or its mutants and an appropriate sgRNAs. The treated cells were analyzed as described in the Examples. Cellular C to T conversion percentages, defined as the percentage of total DNA sequencing reads with Ts at the target positions indicated, are shown (left). Percent of total sequencing reads containing the C to T conversion is shown on the right. The BE3 point mutants do not significantly affect base editing efficiencies at HEK site 4, a site with only one target cytidine.



FIG. 99 shows a comparison of on-target editing plasma delivery in BE3 and HF-BE3.



FIG. 100 shows a comparison of on-target editing in protein and plasma delivery of BE3.



FIG. 101 shows a comparison of on-target editing in protein and plasma delivery of HF-BE3.



FIG. 102 shows that both lipofection and installing HF mutations decrease off-target deamination events. The diamond indicates no off targets were detected and the specificity ratio was set to 100.



FIG. 103 shows in vitro C to T editing on a synthetic substrate with Cs placed at even positions in the protospacer (NNNNTC2TC4TC6TC8TC10TC12TC14TC16TC18TC20NGG, SEQ ID NO: 4272).



FIG. 104 shows in vitro C to T editing on a synthetic substrate with Cs placed at odd positions in the protospacer (NNNNTC2TC4TC6TC8TC10TC12TC14TC16TC18TC20NGG, SEQ ID NO: 4272).



FIG. 105 includes two graphs depicting the specificity ratio of base editing with plasmid vs. protein delivery.



FIGS. 106A to 106B shows BE3 activity on non-NGG PAM sites. HEK293T cells were transfected with plasmids expressing BE3 and appropriate sgRNA. The treated cells were analyzed as described in the Examples. FIG. 106A shows BE3 activity on sites can be efficiently targeted by SaBE3 or SaKKH-BE3. BE3 shows low but significant activity on the NAG PAM. FIG. 106B shows BE3 has significantly reduced editing at sites with NGA or NGCG PAMs, in contrast to VQR-BE3 or VRER-BE3.



FIGS. 107A to 107B show the effect of APOBEC1 mutations on VQR-BE3 and SaKKH-BE3. HEK293T cells were transfected with plasmids expressing VQR-BE3, SaKKH-BE3 or its mutants and an appropriate sgRNAs. The treated cells were analyzed as described in the Methods. Cellular C to T conversion percentages, defined as the percentage of total DNA sequencing reads with Ts at the target positions indicated, are shown. FIG. 107A shows that the window-modulating mutations can be applied to VQR-BE3 to enable selective base editing at sites targetable by NGA PAM. FIG. 107B shows that, when applied to SaKKH-BE3, the mutations cause overall decrease in base editing efficiency without conferring base selectivity within the target window.



FIG. 108 shows a schematic representation of nucleotide editing. The following abbreviations are used: (MMR)—mismatch repair, (BE3 Nickase)—refers to base editor 3, which comprises a Cas9 nickase domain, (UGI)—uracil glycosylase inhibitor, UDG)—uracil DNA glycosylase, (APOBEC)—refers to an APOBEC cytidine deaminase.





DEFINITIONS

As used herein and in the claims, the singular forms “a,” “an,” and “the” include the singular and the plural reference unless the context clearly indicates otherwise. Thus, for example, a reference to “an agent” includes a single agent and a plurality of such agents.


The term “Cas9” or “Cas9 nuclease” refers to an RNA-guided nuclease comprising a Cas9 protein, or a fragment thereof (e.g., a protein comprising an active, inactive, or partially active DNA cleavage domain of Cas9, and/or the gRNA binding domain of Cas9). A Cas9 nuclease is also referred to sometimes as a casn1 nuclease or a CRISPR (clustered regularly interspaced short palindromic repeat)-associated nuclease. CRISPR is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain spacers, sequences complementary to antecedent mobile elements, and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA). In type II CRISPR systems correct processing of pre-crRNA requires a trans-encoded small RNA (tracrRNA), endogenous ribonuclease 3 (rnc) and a Cas9 protein. The tracrRNA serves as a guide for ribonuclease 3-aided processing of pre-crRNA. Subsequently, Cas9/crRNA/tracrRNA endonucleolytically cleaves linear or circular dsDNA target complementary to the spacer. The target strand not complementary to crRNA is first cut endonucleolytically, then trimmed 3′-5′ exonucleolytically. In nature, DNA-binding and cleavage typically requires protein and both RNAs. However, single guide RNAs (“sgRNA”, or simply “gNRA”) can be engineered so as to incorporate aspects of both the crRNA and tracrRNA into a single RNA species. See, e.g., Jinek M., Chylinski K., Fonfara I., Hauer M., Doudna J. A., Charpentier E. Science 337:816-821(2012), the entire contents of which is hereby incorporated by reference. Cas9 recognizes a short motif in the CRISPR repeat sequences (the PAM or protospacer adjacent motif) to help distinguish self versus non-self. Cas9 nuclease sequences and structures are well known to those of skill in the art (see, e.g., “Complete genome sequence of an M1 strain of Streptococcus pyogenes.” Ferretti et al., J. J., McShan W. M., Ajdic D. J., Savic D. J., Savic G., Lyon K., Primeaux C., Sezate S., Suvorov A. N., Kenton S., Lai H. S., Lin S. P., Qian Y., Jia H. G., Najar F. Z., Ren Q., Zhu H., Song L., White J., Yuan X., Clifton S. W., Roe B. A., McLaughlin R. E., Proc. Natl. Acad. Sci. U.S.A. 98:4658-4663(2001); “CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III.” Deltcheva E., Chylinski K., Sharma C. M., Gonzales K., Chao Y., Pirzada Z. A., Eckert M. R., Vogel J., Charpentier E., Nature 471:602-607(2011); and “A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.” Jinek M., Chylinski K., Fonfara I., Hauer M., Doudna J. A., Charpentier E. Science 337:816-821(2012), the entire contents of each of which are incorporated herein by reference). Cas9 orthologs have been described in various species, including, but not limited to, S. pyogenes and S. thermophilus. Additional suitable Cas9 nucleases and sequences will be apparent to those of skill in the art based on this disclosure, and such Cas9 nucleases and sequences include Cas9 sequences from the organisms and loci disclosed in Chylinski, Rhun, and Charpentier, “The tracrRNA and Cas9 families of type II CRISPR-Cas immunity systems” (2013) RNA Biology 10:5, 726-737; the entire contents of which are incorporated herein by reference. In some embodiments, a Cas9 nuclease has an inactive (e.g., an inactivated) DNA cleavage domain, that is, the Cas9 is a nickase.


A nuclease-inactivated Cas9 protein may interchangeably be referred to as a “dCas9” protein (for nuclease-“dead” Cas9). Methods for generating a Cas9 protein (or a fragment thereof) having an inactive DNA cleavage domain are known (See, e.g., Jinek et al., Science. 337:816-821(2012); Qi et al., “Repurposing CRISPR as an RNA-Guided Platform for Sequence-Specific Control of Gene Expression” (2013) Cell. 28; 152(5):1173-83, the entire contents of each of which are incorporated herein by reference). For example, the DNA cleavage domain of Cas9 is known to include two subdomains, the HNH nuclease subdomain and the RuvC1 subdomain. The HNH subdomain cleaves the strand complementary to the gRNA, whereas the RuvC1 subdomain cleaves the non-complementary strand. Mutations within these subdomains can silence the nuclease activity of Cas9. For example, the mutations D10A and H840A completely inactivate the nuclease activity of S. pyogenes Cas9 (Jinek et al., Science. 337:816-821(2012); Qi et al., Cell. 28; 152(5):1173-83 (2013)). In some embodiments, proteins comprising fragments of Cas9 are provided. For example, in some embodiments, a protein comprises one of two Cas9 domains: (1) the gRNA binding domain of Cas9; or (2) the DNA cleavage domain of Cas9. In some embodiments, proteins comprising Cas9 or fragments thereof are referred to as “Cas9 variants.” A Cas9 variant shares homology to Cas9, or a fragment thereof. For example a Cas9 variant is at least about 70% identical, at least about 80% identical, at least about 90% identical, at least about 95% identical, at least about 96% identical, at least about 97% identical, at least about 98% identical, at least about 99% identical, at least about 99.5% identical, or at least about 99.9% identical to wild type Cas9. In some embodiments, the Cas9 variant may have 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 21, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 or more amino acid changes compared to wild type Cas9. In some embodiments, the Cas9 variant comprises a fragment of Cas9 (e.g., a gRNA binding domain or a DNA-cleavage domain), such that the fragment is at least about 70% identical, at least about 80% identical, at least about 90% identical, at least about 95% identical, at least about 96% identical, at least about 97% identical, at least about 98% identical, at least about 99% identical, at least about 99.5% identical, or at least about 99.9% identical to the corresponding fragment of wild type Cas9. In some embodiments, the fragment is is at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95% identical, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% of the amino acid length of a corresponding wild type Cas9.


In some embodiments, the fragment is at least 100 amino acids in length. In some embodiments, the fragment is at least 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1050, 1100, 1150, 1200, 1250, or at least 1300 amino acids in length. In some embodiments, wild type Cas9 corresponds to Cas9 from Streptococcus pyogenes (NCBI Reference Sequence: NC_017053.1, SEQ ID NO:1 (nucleotide); SEQ ID NO:2 (amino acid)).









(SEQ ID NO: 1)


ATGGATAAGAAATACTCAATAGGCTTAGATATCGGCACAAATAGCGTCGGA





TGGGCGGTGATCACTGATGATTATAAGGTTCCGTCTAAAAAGTTCAAGGTT





CTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTT





TTATTTGGCAGTGGAGAGACAGCGGAAGCGACTCGTCTCAAACGGACAGCT





CGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATT





TTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAA





GAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTT





GGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAACTATCTAT





CATCTGCGAAAAAAATTGGCAGATTCTACTGATAAAGCGGATTTGCGCTTA





ATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTTTGATT





GAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAG





TTGGTACAAATCTACAATCAATTATTTGAAGAAAACCCTATTAACGCAAGT





AGAGTAGATGCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGACGA





TTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGAGAAATGGCTTGTTT





GGGAATCTCATTGCTTTGTCATTGGGATTGACCCCTAATTTTAAATCAAAT





TTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGAT





GATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTG





TTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTA





AGAGTAAATAGTGAAATAACTAAGGCTCCCCTATCAGCTTCAATGATTAAG





CGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGA





CAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAAC





GGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAA





TTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGTG





AAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGC





TCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTTTGAGAAGA





CAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAA





ATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAAT





AGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGG





AATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAA





CGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAA





CATAGTTTGCTTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTC





AAATATGTTACTGAGGGAATGCGAAAACCAGCATTTCTTTCAGGTGAACAG





AAGAAAGCCATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTT





AAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTT





GAAATTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGCGCCTACCAT





GATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGGATAATGAAGAAAAT





GAAGATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGG





GGGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAG





GTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCT





CGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTA





GATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATC





CATGATGATAGTTTGACATTTAAAGAAGATATTCAAAAAGCACAGGTGTCT





GGACAAGGCCATAGTTTACATGAACAGATTGCTAACTTAGCTGGCAGTCCT





GCTATTAAAAAAGGTATTTTACAGACTGTAAAAATTGTTGATGAACTGGTC





AAAGTAATGGGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAA





AATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGAGAGCGTATGAAACGA





ATCGAAGAAGGTATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCATCCT





GTTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTCTATTATCTACAA





AATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAAGT





GATTATGATGTCGATCACATTGTTCCACAAAGTTTCATTAAAGACGATTCA





ATAGACAATAAGGTACTAACGCGTTCTGATAAAAATCGTGGTAAATCGGAT





AACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAAACTATTGGAGACAA





CTTCTAAACGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAACGAAA





GCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGC





CAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGAT





AGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTT





AAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTC





CAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCG





TATCTAAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAACTT





GAATCGGAGTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAATG





ATTGCTAAGTCTGAGCAAGAAATAGGCAAAGCAACCGCAAAATATTTCTTT





TACTCTAATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGA





GAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATT





GTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATG





CCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCC





AAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAA





AAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCT





TATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTA





AAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTT





GAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTTAAA





AAAGACTTAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAAAAC





GGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAAAAAGGAAATGAG





CTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTAT





GAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTG





GAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTT





TCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCA





TATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAATATTATT





CATTTATTTACGTTGACGAATCTTGGAGCTCCCGCTGCTTTTAAATATTTT





GATACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGAT





GCCACTCTTATCCATCAATCCATCACTGGTCTTTATGAAACACGCATTGAT





TTGAGTCAGCTAGGAGGTGACTGA





(SEQ ID NO: 2)


MDKKYSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGAL






LFGSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLE






ESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLADSTDKADLRL





IYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQIYNQLFEENPINAS





RVDAKAILSARLSKSRRLENLIAQLPGEKRNGLFGNLIALSLGLTPNFKSN





FDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDIL





RVNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKN





GYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRTFDNG





SIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGN





SRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPK





HSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTV





KQLKEDYFKKIECFDSVEISGVEDRFNASLGAYHDLLKIIKDKDFLDNEEN





EDILEDIVLTLTLFEDRGMIEERLKTYAHLFDDKVMKQLKRRRYTGWGRLS





RKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKEDIQKAQVS





GQGHSLHEQIANLAGSPAIKKGILQTVKIVDELVKVMGHKPENIVIEMARE





NQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQ






NGRDMYVDQELDINRLSDYDVDHIVPQSFIKDDSIDNKVLTRSDKNRGKSD







NVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERGGLSELDKAGFIKR







QLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKDF







QFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKM







IAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEI







VWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARK






KDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSSF





EKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGNE





LALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISEF





SKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYF





DTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD


(single underline: HNH domain; double underline:


RuvC domain)






In some embodiments, wild type Cas9 corresponds to, or comprises SEQ ID NO:3 (nucleotide) and/or SEQ ID NO: 4 (amino acid):









(SEQ ID NO: 3)


ATGGATAAAAAGTATTCTATTGGTTTAGACATCGGCACTAATTCCGTTGGA





TGGGCTGTCATAACCGATGAATACAAAGTACCTTCAAAGAAATTTAAGGTG





TTGGGGAACACAGACCGTCATTCGATTAAAAAGAATCTTATCGGTGCCCTC





CTATTCGATAGTGGCGAAACGGCAGAGGCGACTCGCCTGAAACGAACCGCT





CGGAGAAGGTATACACGTCGCAAGAACCGAATATGTTACTTACAAGAAATT





TTTAGCAATGAGATGGCCAAAGTTGACGATTCTTTCTTTCACCGTTTGGAA





GAGTCCTTCCTTGTCGAAGAGGACAAGAAACATGAACGGCACCCCATCTTT





GGAAACATAGTAGATGAGGTGGCATATCATGAAAAGTACCCAACGATTTAT





CACCTCAGAAAAAAGCTAGTTGACTCAACTGATAAAGCGGACCTGAGGTTA





ATCTACTTGGCTCTTGCCCATATGATAAAGTTCCGTGGGCACTTTCTCATT





GAGGGTGATCTAAATCCGGACAACTCGGATGTCGACAAACTGTTCATCCAG





TTAGTACAAACCTATAATCAGTTGTTTGAAGAGAACCCTATAAATGCAAGT





GGCGTGGATGCGAAGGCTATTCTTAGCGCCCGCCTCTCTAAATCCCGACGG





CTAGAAAACCTGATCGCACAATTACCCGGAGAGAAGAAAAATGGGTTGTTC





GGTAACCTTATAGCGCTCTCACTAGGCCTGACACCAAATTTTAAGTCGAAC





TTCGACTTAGCTGAAGATGCCAAATTGCAGCTTAGTAAGGACACGTACGAT





GACGATCTCGACAATCTACTGGCACAAATTGGAGATCAGTATGCGGACTTA





TTTTTGGCTGCCAAAAACCTTAGCGATGCAATCCTCCTATCTGACATACTG





AGAGTTAATACTGAGATTACCAAGGCGCCGTTATCCGCTTCAATGATCAAA





AGGTACGATGAACATCACCAAGACTTGACACTTCTCAAGGCCCTAGTCCGT





CAGCAACTGCCTGAGAAATATAAGGAAATATTCTTTGATCAGTCGAAAAAC





GGGTACGCAGGTTATATTGACGGCGGAGCGAGTCAAGAGGAATTCTACAAG





TTTATCAAACCCATATTAGAGAAGATGGATGGGACGGAAGAGTTGCTTGTA





AAACTCAATCGCGAAGATCTACTGCGAAAGCAGCGGACTTTCGACAACGGT





AGCATTCCACATCAAATCCACTTAGGCGAATTGCATGCTATACTTAGAAGG





CAGGAGGATTTTTATCCGTTCCTCAAAGACAATCGTGAAAAGATTGAGAAA





ATCCTAACCTTTCGCATACCTTACTATGTGGGACCCCTGGCCCGAGGGAAC





TCTCGGTTCGCATGGATGACAAGAAAGTCCGAAGAAACGATTACTCCATGG





AATTTTGAGGAAGTTGTCGATAAAGGTGCGTCAGCTCAATCGTTCATCGAG





AGGATGACCAACTTTGACAAGAATTTACCGAACGAAAAAGTATTGCCTAAG





CACAGTTTACTTTACGAGTATTTCACAGTGTACAATGAACTCACGAAAGTT





AAGTATGTCACTGAGGGCATGCGTAAACCCGCCTTTCTAAGCGGAGAACAG





AAGAAAGCAATAGTAGATCTGTTATTCAAGACCAACCGCAAAGTGACAGTT





AAGCAATTGAAAGAGGACTACTTTAAGAAAATTGAATGCTTCGATTCTGTC





GAGATCTCCGGGGTAGAAGATCGATTTAATGCGTCACTTGGTACGTATCAT





GACCTCCTAAAGATAATTAAAGATAAGGACTTCCTGGATAACGAAGAGAAT





GAAGATATCTTAGAAGATATAGTGTTGACTCTTACCCTCTTTGAAGATCGG





GAAATGATTGAGGAAAGACTAAAAACATACGCTCACCTGTTCGACGATAAG





GTTATGAAACAGTTAAAGAGGCGTCGCTATACGGGCTGGGGACGATTGTCG





CGGAAACTTATCAACGGGATAAGAGACAAGCAAAGTGGTAAAACTATTCTC





GATTTTCTAAAGAGCGACGGCTTCGCCAATAGGAACTTTATGCAGCTGATC





CATGATGACTCTTTAACCTTCAAAGAGGATATACAAAAGGCACAGGTTTCC





GGACAAGGGGACTCATTGCACGAACATATTGCGAATCTTGCTGGTTCGCCA





GCCATCAAAAAGGGCATACTCCAGACAGTCAAAGTAGTGGATGAGCTAGTT





AAGGTCATGGGACGTCACAAACCGGAAAACATTGTAATCGAGATGGCACGC





GAAAATCAAACGACTCAGAAGGGGCAAAAAAACAGTCGAGAGCGGATGAAG





AGAATAGAAGAGGGTATTAAAGAACTGGGCAGCCAGATCTTAAAGGAGCAT





CCTGTGGAAAATACCCAATTGCAGAACGAGAAACTTTACCTCTATTACCTA





CAAAATGGAAGGGACATGTATGTTGATCAGGAACTGGACATAAACCGTTTA





TCTGATTACGACGTCGATCACATTGTACCCCAATCCTTTTTGAAGGACGAT





TCAATCGACAATAAAGTGCTTACACGCTCGGATAAGAACCGAGGGAAAAGT





GACAATGTTCCAAGCGAGGAAGTCGTAAAGAAAATGAAGAACTATTGGCGG





CAGCTCCTAAATGCGAAACTGATAACGCAAAGAAAGTTCGATAACTTAACT





AAAGCTGAGAGGGGTGGCTTGTCTGAACTTGACAAGGCCGGATTTATTAAA





CGTCAGCTCGTGGAAACCCGCCAAATCACAAAGCATGTTGCACAGATACTA





GATTCCCGAATGAATACGAAATACGACGAGAACGATAAGCTGATTCGGGAA





GTCAAAGTAATCACTTTAAAGTCAAAATTGGTGTCGGACTTCAGAAAGGAT





TTTCAATTCTATAAAGTTAGGGAGATAAATAACTACCACCATGCGCACGAC





GCTTATCTTAATGCCGTCGTAGGGACCGCACTCATTAAGAAATACCCGAAG





CTAGAAAGTGAGTTTGTGTATGGTGATTACAAAGTTTATGACGTCCGTAAG





ATGATCGCGAAAAGCGAACAGGAGATAGGCAAGGCTACAGCCAAATACTTC





TTTTATTCTAACATTATGAATTTCTTTAAGACGGAAATCACTCTGGCAAAC





GGAGAGATACGCAAACGACCTTTAATTGAAACCAATGGGGAGACAGGTGAA





ATCGTATGGGATAAGGGCCGGGACTTCGCGACGGTGAGAAAAGTTTTGTCC





ATGCCCCAAGTCAACATAGTAAAGAAAACTGAGGTGCAGACCGGAGGGTTT





TCAAAGGAATCGATTCTTCCAAAAAGGAATAGTGATAAGCTCATCGCTCGT





AAAAAGGACTGGGACCCGAAAAAGTACGGTGGCTTCGATAGCCCTACAGTT





GCCTATTCTGTCCTAGTAGTGGCAAAAGTTGAGAAGGGAAAATCCAAGAAA





CTGAAGTCAGTCAAAGAATTATTGGGGATAACGATTATGGAGCGCTCGTCT





TTTGAAAAGAACCCCATCGACTTCCTTGAGGCGAAAGGTTACAAGGAAGTA





AAAAAGGATCTCATAATTAAACTACCAAAGTATAGTCTGTTTGAGTTAGAA





AATGGCCGAAAACGGATGTTGGCTAGCGCCGGAGAGCTTCAAAAGGGGAAC





GAACTCGCACTACCGTCTAAATACGTGAATTTCCTGTATTTAGCGTCCCAT





TACGAGAAGTTGAAAGGTTCACCTGAAGATAACGAACAGAAGCAACTTTTT





GTTGAGCAGCACAAACATTATCTCGACGAAATCATAGAGCAAATTTCGGAA





TTCAGTAAGAGAGTCATCCTAGCTGATGCCAATCTGGACAAAGTATTAAGC





GCATACAACAAGCACAGGGATAAACCCATACGTGAGCAGGCGGAAAATATT





ATCCATTTGTTTACTCTTACCAACCTCGGCGCTCCAGCCGCATTCAAGTAT





TTTGACACAACGATAGATCGCAAACGATACACTTCTACCAAGGAGGTGCTA





GACGCGACACTGATTCACCAATCCATCACGGGATTATATGAAACTCGGATA





GATTTGTCACAGCTTGGGGGTGACGGATCCCCCAAGAAGAAGAGGAAAGTC





TCGAGCGACTACAAAGACCATGACGGTGATTATAAAGATCATGACATCGAT





TACAAGGATGACGATGACAAGGCTGCAGGA





(SEQ ID NO: 4)


MDKKYSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGAL






LFDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLE






ESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRL





IYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPINAS





GVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSN





FDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDIL





RVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKN





GYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRTFDNG





SIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGN





SRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPK





HSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTV





KQLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEEN





EDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWGRLS





RKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKEDIQKAQVS





GQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMAR





ENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYL






QNGRDMYVDQELDINRLSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKS







DNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERGGLSELDKAGFIK







RQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKD







FQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRK







MIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGE







IVWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIAR






KKDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSS





FEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGN





ELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISE





FSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKY





FDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD


(single underline: HNH domain; double underline:


RuvC domain)






In some embodiments, wild type Cas9 corresponds to Cas9 from Streptococcus pyogenes (NCBI Reference Sequence: NC_002737.2, SEQ ID NO: 8 (nucleotide); and Uniport Reference Sequence: Q99ZW2, SEQ ID NO: 10 (amino acid).









(SEQ ID NO: 8)


ATGGATAAGAAATACTCAATAGGCTTAGATATCGGCACAAATAGCGTCGGA





TGGGCGGTGATCACTGATGAATATAAGGTTCCGTCTAAAAAGTTCAAGGTT





CTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTT





TTATTTGACAGTGGAGAGACAGCGGAAGCGACTCGTCTCAAACGGACAGCT





CGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATT





TTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAA





GAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTT





GGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAACTATCTAT





CATCTGCGAAAAAAATTGGTAGATTCTACTGATAAAGCGGATTTGCGCTTA





ATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTTTGATT





GAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAG





TTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCTATTAACGCAAGT





GGAGTAGATGCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGACGA





TTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGAAAAATGGCTTATTT





GGGAATCTCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATCAAAT





TTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGAT





GATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTG





TTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTA





AGAGTAAATACTGAAATAACTAAGGCTCCCCTATCAGCTTCAATGATTAAA





CGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGA





CAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAAC





GGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAA





TTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGTG





AAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGC





TCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTTTGAGAAGA





CAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAA





ATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAAT





AGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGG





AATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAA





CGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAA





CATAGTTTGCTTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTC





AAATATGTTACTGAAGGAATGCGAAAACCAGCATTTCTTTCAGGTGAACAG





AAGAAAGCCATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTT





AAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTT





GAAATTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCAT





GATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGGATAATGAAGAAAAT





GAAGATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGG





GAGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAG





GTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCT





CGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTA





GATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATC





CATGATGATAGTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGTCT





GGACAAGGCGATAGTTTACATGAACATATTGCAAATTTAGCTGGTAGCCCT





GCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTC





AAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGT





GAAAATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGAGAGCGTATGAAA





CGAATCGAAGAAGGTATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCAT





CCTGTTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTCTATTATCTC





CAAAATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTA





AGTGATTATGATGTCGATCACATTGTTCCACAAAGTTTCCTTAAAGACGAT





TCAATAGACAATAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCG





GATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAAACTATTGGAGA





CAACTTCTAAACGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAACG





AAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAA





CGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTG





GATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAG





GTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGAT





TTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGAT





GCGTATCTAAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAA





CTTGAATCGGAGTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAA





ATGATTGCTAAGTCTGAGCAAGAAATAGGCAAAGCAACCGCAAAATATTTC





TTTTACTCTAATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAAT





GGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAA





ATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCC





ATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTC





TCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGT





AAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTA





GCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAG





TTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCC





TTTGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTT





AAAAAAGACTTAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAA





AACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAAAAAGGAAAT





GAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCAT





TATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTT





GTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAA





TTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGT





GCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAATATT





ATTCATTTATTTACGTTGACGAATCTTGGAGCTCCCGCTGCTTTTAAATAT





TTTGATACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTA





GATGCCACTCTTATCCATCAATCCATCACTGGTCTTTATGAAACACGCATT





GATTTGAGTCAGCTAGGAGGTGACTGA





(SEQ ID NO: 10)


MDKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGAL






LFDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLE






ESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRL





IYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPINAS





GVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSN





FDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDIL





RVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKN





GYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRTFDNG





SIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGN





SRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPK





HSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTV





KQLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEEN





EDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWGRLS





RKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKEDIQKAQVS





GQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMAR





ENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYL






QNGRDMYVDQELDINRLSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKS







DNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERGGLSELDKAGFIK







RQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKD







FQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRK







MIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGE







IVWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIAR






KKDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSS





FEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGN





ELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISE





FSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKY





FDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD


(single underline: HNH domain; double underline:


RuvC domain)






In some embodiments, Cas9 refers to Cas9 from: Corynebacterium ulcerans (NCBI Refs: NC_015683.1, NC_017317.1); Corynebacterium diphtheria (NCBI Refs: NC_016782.1, NC_016786.1); Spiroplasma syrphidicola (NCBI Ref: NC_021284.1); Prevotella intermedia (NCBI Ref: NC_017861.1); Spiroplasma taiwanense (NCBI Ref: NC_021846.1); Streptococcus iniae (NCBI Ref: NC_021314.1); Belliella baltica (NCBI Ref: NC_018010.1); Psychroflexus torquisI (NCBI Ref: NC_018721.1); Streptococcus thermophilus (NCBI Ref: YP_820832.1), Listeria innocua (NCBI Ref: NP_472073.1), Campylobacter jejuni (NCBI Ref: YP_002344900.1) or Neisseria. meningitidis (NCBI Ref: YP_002342100.1) or to a Cas9 from any of the organisms listed in Example 5.


In some embodiments, dCas9 corresponds to, or comprises in part or in whole, a Cas9 amino acid sequence having one or more mutations that inactivate the Cas9 nuclease activity. For example, in some embodiments, a dCas9 domain comprises D10A and/or H840A mutation. dCas9 (D10A and H840A):










(SEQ ID NO: 9)



MDKKYSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDS








GET
AEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKK






HERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLI





EGDLNPDNSDVDKLFIQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLENLIAQ





LPGEKKNGLFGNLIALSLGLTPNFKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIGDQ





YADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQL





PEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRK





QRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSR





FAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYF





TVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIEC





FDSVETSGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMIEE





RLKTYAHLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFAN







embedded image









embedded image









NTQLCINEKLYLYYLCINGRDMYVDQELDINRLSDYDVDAIVPQSFLKDDSIDNKV









embedded image









embedded image









embedded image









embedded image









embedded image







TVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLI





IKLPKYSLFELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDN





EQKQLFVEQHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIH





LFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD


(single underline: HNH domain; double underline: RuvC domain).






In some embodiments, the Cas9 domain comprises a D10A mutation, while the residue at position 840 remains a histidine in the amino acid sequence provided in SEQ ID NO: 10, or at corresponding positions in any of the amino acid sequences provided in SEQ ID NOs: 11-260. Without wishing to be bound by any particular theory, the presence of the catalytic residue H840 restores the acvitity of the Cas9 to cleave the non-edited (e.g., non-deaminated) strand containing a G opposite the targeted C. Restoration of H840 (e.g., from A840) does not result in the cleavage of the target strand containing the C. Such Cas9 variants are able to generate a single-strand DNA break (nick) at a specific location based on the gRNA-defined target sequence, leading to repair of the non-edited strand, ultimately resulting in a G to A change on the non-edited strand. A schematic representation of this process is shown in FIG. 108. Briefly, the C of a C-G basepair can be deaminated to a U by a deaminase, e.g., an APOBEC deamonase. Nicking the non-edited strand, having the G, facilitates removal of the G via mismatch repair mechanisms. UGI inhibits UDG, which prevents removal of the U.


In other embodiments, dCas9 variants having mutations other than D10A and H840A are provided, which, e.g., result in nuclease inactivated Cas9 (dCas9). Such mutations, by way of example, include other amino acid substitutions at D10 and H820, or other substitutions within the nuclease domains of Cas9 (e.g., substitutions in the HNH nuclease subdomain and/or the RuvC1 subdomain). In some embodiments, variants or homologues of dCas9 (e.g., variants of SEQ ID NO: 10) are provided which are at least about 70% identical, at least about 80% identical, at least about 90% identical, at least about 95% identical, at least about 98% identical, at least about 99% identical, at least about 99.5% identical, or at least about 99.9% identical to SEQ ID NO: 10. In some embodiments, variants of dCas9 (e.g., variants of SEQ ID NO: 10) are provided having amino acid sequences which are shorter, or longer than SEQ ID NO: 10, by about 5 amino acids, by about 10 amino acids, by about 15 amino acids, by about 20 amino acids, by about 25 amino acids, by about 30 amino acids, by about 40 amino acids, by about 50 amino acids, by about 75 amino acids, by about 100 amino acids or more.


In some embodiments, Cas9 fusion proteins as provided herein comprise the full-length amino acid sequence of a Cas9 protein, e.g., one of the Cas9 sequences provided herein. In other embodiments, however, fusion proteins as provided herein do not comprise a full-length Cas9 sequence, but only a fragment thereof. For example, in some embodiments, a Cas9 fusion protein provided herein comprises a Cas9 fragment, wherein the fragment binds crRNA and tracrRNA or sgRNA, but does not comprise a functional nuclease domain, e.g., in that it comprises only a truncated version of a nuclease domain or no nuclease domain at all. Exemplary amino acid sequences of suitable Cas9 domains and Cas9 fragments are provided herein, and additional suitable sequences of Cas9 domains and fragments will be apparent to those of skill in the art.


In some embodiments, Cas9 refers to Cas9 from: Corynebacterium ulcerans (NCBI Refs: NC_015683.1, NC_017317.1); Corynebacterium diphtheria (NCBI Refs: NC_016782.1, NC_016786.1); Spiroplasma syrphidicola (NCBI Ref: NC_021284.1); Prevotella intermedia (NCBI Ref: NC_017861.1); Spiroplasma taiwanense (NCBI Ref: NC_021846.1); Streptococcus iniae (NCBI Ref: NC_021314.1); Belliella baltica (NCBI Ref: NC_018010.1); Psychroflexus torquisI (NCBI Ref: NC_018721.1); Streptococcus thermophilus (NCBI Ref: YP_820832.1); Listeria innocua (NCBI Ref: NP_472073.1); Campylobacter jejuni (NCBI Ref: YP_002344900.1); or Neisseria. meningitidis (NCBI Ref: YP_002342100.1).


The term “deaminase” or “deaminase domain,” as used herein, refers to a protein or enzyme that catalyzes a deamination reaction. In some embodiments, the deaminase or deaminase domain is a cytidine deaminase, catalyzing the hydrolytic deamination of cytidine or deoxycytidine to uridine or deoxyuridine, respectively. In some embodiments, the deaminase or deaminase domain is a cytidine deaminase domain, catalyzing the hydrolytic deamination of cytosine to uracil. In some embodiments, the deaminase or deaminase domain is a naturally-occurring deaminase from an organism, such as a human, chimpanzee, gorilla, monkey, cow, dog, rat, or mouse. In some embodiments, the deaminase or deaminase domain is a variant of a naturally-occurring deaminase from an organism, that does not occur in nature. For example, in some embodiments, the deaminase or deaminase domain is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75% at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to a naturally-occurring deaminase from an organism.


The term “effective amount,” as used herein, refers to an amount of a biologically active agent that is sufficient to elicit a desired biological response. For example, in some embodiments, an effective amount of a nuclease may refer to the amount of the nuclease that is sufficient to induce cleavage of a target site specifically bound and cleaved by the nuclease. In some embodiments, an effective amount of a fusion protein provided herein, e.g., of a fusion protein comprising a nuclease-inactive Cas9 domain and a nucleic acid editing domain (e.g., a deaminase domain) may refer to the amount of the fusion protein that is sufficient to induce editing of a target site specifically bound and edited by the fusion protein. As will be appreciated by the skilled artisan, the effective amount of an agent, e.g., a fusion protein, a nuclease, a deaminase, a recombinase, a hybrid protein, a protein dimer, a complex of a protein (or protein dimer) and a polynucleotide, or a polynucleotide, may vary depending on various factors as, for example, on the desired biological response, e.g., on the specific allele, genome, or target site to be edited, on the cell or tissue being targeted, and on the agent being used.


The term “linker,” as used herein, refers to a chemical group or a molecule linking two molecules or moieties, e.g., two domains of a fusion protein, such as, for example, a nuclease-inactive Cas9 domain and a nucleic acid editing domain (e.g., a deaminase domain). In some embodiments, a linker joins a gRNA binding domain of an RNA-programmable nuclease, including a Cas9 nuclease domain, and the catalytic domain of a nucleic-acid editing protein. In some embodiments, a linker joins a dCas9 and a nucleic-acid editing protein. Typically, the linker is positioned between, or flanked by, two groups, molecules, or other moieties and connected to each one via a covalent bond, thus connecting the two. In some embodiments, the linker is an amino acid or a plurality of amino acids (e.g., a peptide or protein). In some embodiments, the linker is an organic molecule, group, polymer, or chemical moiety. In some embodiments, the linker is 5-100 amino acids in length, for example, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 30-35, 35-40, 40-45, 45-50, 50-60, 60-70, 70-80, 80-90, 90-100, 100-150, or 150-200 amino acids in length. Longer or shorter linkers are also contemplated.


The term “mutation,” as used herein, refers to a substitution of a residue within a sequence, e.g., a nucleic acid or amino acid sequence, with another residue, or a deletion or insertion of one or more residues within a sequence. Mutations are typically described herein by identifying the original residue followed by the position of the residue within the sequence and by the identity of the newly substituted residue. Various methods for making the amino acid substitutions (mutations) provided herein are well known in the art, and are provided by, for example, Green and Sambrook, Molecular Cloning: A Laboratory Manual (4th ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (2012)).


The terms “nucleic acid” and “nucleic acid molecule,” as used herein, refer to a compound comprising a nucleobase and an acidic moiety, e.g., a nucleoside, a nucleotide, or a polymer of nucleotides. Typically, polymeric nucleic acids, e.g., nucleic acid molecules comprising three or more nucleotides are linear molecules, in which adjacent nucleotides are linked to each other via a phosphodiester linkage. In some embodiments, “nucleic acid” refers to individual nucleic acid residues (e.g. nucleotides and/or nucleosides). In some embodiments, “nucleic acid” refers to an oligonucleotide chain comprising three or more individual nucleotide residues. As used herein, the terms “oligonucleotide” and “polynucleotide” can be used interchangeably to refer to a polymer of nucleotides (e.g., a string of at least three nucleotides). In some embodiments, “nucleic acid” encompasses RNA as well as single and/or double-stranded DNA. Nucleic acids may be naturally occurring, for example, in the context of a genome, a transcript, an mRNA, tRNA, rRNA, siRNA, snRNA, a plasmid, cosmid, chromosome, chromatid, or other naturally occurring nucleic acid molecule. On the other hand, a nucleic acid molecule may be a non-naturally occurring molecule, e.g., a recombinant DNA or RNA, an artificial chromosome, an engineered genome, or fragment thereof, or a synthetic DNA, RNA, DNA/RNA hybrid, or including non-naturally occurring nucleotides or nucleosides. Furthermore, the terms “nucleic acid,” “DNA,” “RNA,” and/or similar terms include nucleic acid analogs, e.g., analogs having other than a phosphodiester backbone. Nucleic acids can be purified from natural sources, produced using recombinant expression systems and optionally purified, chemically synthesized, etc. Where appropriate, e.g., in the case of chemically synthesized molecules, nucleic acids can comprise nucleoside analogs such as analogs having chemically modified bases or sugars, and backbone modifications. A nucleic acid sequence is presented in the 5′ to 3′ direction unless otherwise indicated. In some embodiments, a nucleic acid is or comprises natural nucleosides (e.g. adenosine, thymidine, guanosine, cytidine, uridine, deoxyadenosine, deoxythymidine, deoxyguanosine, and deoxycytidine); nucleoside analogs (e.g., 2-aminoadenosine, 2-thiothymidine, inosine, pyrrolo-pyrimidine, 3-methyl adenosine, 5-methylcytidine, 2-aminoadenosine, C5-bromouridine, C5-fluorouridine, C5-iodouridine, C5-propynyl-uridine, C5-propynyl-cytidine, C5-methylcytidine, 2-aminoadenosine, 7-deazaadenosine, 7-deazaguanosine, 8-oxoadenosine, 8-oxoguanosine, O(6)-methylguanine, and 2-thiocytidine); chemically modified bases; biologically modified bases (e.g., methylated bases); intercalated bases; modified sugars (e.g., 2′-fluororibose, ribose, 2′-deoxyribose, arabinose, and hexose); and/or modified phosphate groups (e.g., phosphorothioates and 5′-N-phosphoramidite linkages).


The term “nucleic acid editing domain,” as used herein refers to a protein or enzyme capable of making one or more modifications (e.g., deamination of a cytidine residue) to a nucleic acid (e.g., DNA or RNA). Exemplary nucleic acid editing domains include, but are not limited to a deaminase, a nuclease, a nickase, a recombinase, a methyltransferase, a methylase, an acetylase, an acetyltransferase, a transcriptional activator, or a transcriptional repressor domain. In some embodiments the nucleic acid editing domain is a deaminase (e.g., a cytidine deaminase, such as an APOBEC or an AID deaminase).


The term “proliferative disease,” as used herein, refers to any disease in which cell or tissue homeostasis is disturbed in that a cell or cell population exhibits an abnormally elevated proliferation rate. Proliferative diseases include hyperproliferative diseases, such as pre-neoplastic hyperplastic conditions and neoplastic diseases. Neoplastic diseases are characterized by an abnormal proliferation of cells and include both benign and malignant neoplasias. Malignant neoplasia is also referred to as cancer.


The terms “protein,” “peptide,” and “polypeptide” are used interchangeably herein, and refer to a polymer of amino acid residues linked together by peptide (amide) bonds. The terms refer to a protein, peptide, or polypeptide of any size, structure, or function. Typically, a protein, peptide, or polypeptide will be at least three amino acids long. A protein, peptide, or polypeptide may refer to an individual protein or a collection of proteins. One or more of the amino acids in a protein, peptide, or polypeptide may be modified, for example, by the addition of a chemical entity such as a carbohydrate group, a hydroxyl group, a phosphate group, a farnesyl group, an isofarnesyl group, a fatty acid group, a linker for conjugation, functionalization, or other modification, etc. A protein, peptide, or polypeptide may also be a single molecule or may be a multi-molecular complex. A protein, peptide, or polypeptide may be just a fragment of a naturally occurring protein or peptide. A protein, peptide, or polypeptide may be naturally occurring, recombinant, or synthetic, or any combination thereof. The term “fusion protein” as used herein refers to a hybrid polypeptide which comprises protein domains from at least two different proteins. One protein may be located at the amino-terminal (N-terminal) portion of the fusion protein or at the carboxy-terminal (C-terminal) protein thus forming an “amino-terminal fusion protein” or a “carboxy-terminal fusion protein,” respectively. A protein may comprise different domains, for example, a nucleic acid binding domain (e.g., the gRNA binding domain of Cas9 that directs the binding of the protein to a target site) and a nucleic acid cleavage domain or a catalytic domain of a nucleic-acid editing protein. In some embodiments, a protein comprises a proteinaceous part, e.g., an amino acid sequence constituting a nucleic acid binding domain, and an organic compound, e.g., a compound that can act as a nucleic acid cleavage agent. In some embodiments, a protein is in a complex with, or is in association with, a nucleic acid, e.g., RNA. Any of the proteins provided herein may be produced by any method known in the art. For example, the proteins provided herein may be produced via recombinant protein expression and purification, which is especially suited for fusion proteins comprising a peptide linker. Methods for recombinant protein expression and purification are well known, and include those described by Green and Sambrook, Molecular Cloning: A Laboratory Manual (4th ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (2012)), the entire contents of which are incorporated herein by reference.


The term “RNA-programmable nuclease,” and “RNA-guided nuclease” are used interchangeably herein and refer to a nuclease that forms a complex with (e.g., binds or associates with) one or more RNA that is not a target for cleavage. In some embodiments, an RNA-programmable nuclease, when in a complex with an RNA, may be referred to as a nuclease:RNA complex. Typically, the bound RNA(s) is referred to as a guide RNA (gRNA). gRNAs can exist as a complex of two or more RNAs, or as a single RNA molecule. gRNAs that exist as a single RNA molecule may be referred to as single-guide RNAs (sgRNAs), though “gRNA” is used interchangeably to refer to guide RNAs that exist as either single molecules or as a complex of two or more molecules. Typically, gRNAs that exist as single RNA species comprise two domains: (1) a domain that shares homology to a target nucleic acid (e.g., and directs binding of a Cas9 complex to the target); and (2) a domain that binds a Cas9 protein. In some embodiments, domain (2) corresponds to a sequence known as a tracrRNA, and comprises a stem-loop structure. For example, in some embodiments, domain (2) is identical or homologous to a tracrRNA as provided in Jinek et al., Science 337:816-821(2012), the entire contents of which is incorporated herein by reference. Other examples of gRNAs (e.g., those including domain 2) can be found in U.S. Provisional Patent Application, U.S. Ser. No. 61/874,682, filed Sep. 6, 2013, entitled “Switchable Cas9 Nucleases And Uses Thereof,” and U.S. Provisional Patent Application, U.S. Ser. No. 61/874,746, filed Sep. 6, 2013, entitled “Delivery System For Functional Nucleases,” the entire contents of each are hereby incorporated by reference in their entirety. In some embodiments, a gRNA comprises two or more of domains (1) and (2), and may be referred to as an “extended gRNA.” For example, an extended gRNA will, e.g., bind two or more Cas9 proteins and bind a target nucleic acid at two or more distinct regions, as described herein. The gRNA comprises a nucleotide sequence that complements a target site, which mediates binding of the nuclease/RNA complex to said target site, providing the sequence specificity of the nuclease:RNA complex. In some embodiments, the RNA-programmable nuclease is the (CRISPR-associated system) Cas9 endonuclease, for example Cas9 (Csn1) from Streptococcus pyogenes (see, e.g., “Complete genome sequence of an M1 strain of Streptococcus pyogenes.” Ferretti J. J., McShan W. M., Ajdic D. J., Savic D. J., Savic G., Lyon K., Primeaux C., Sezate S., Suvorov A. N., Kenton S., Lai H. S., Lin S. P., Qian Y., Jia H. G., Najar F. Z., Ren Q., Zhu H., Song L., White J., Yuan X., Clifton S. W., Roe B. A., McLaughlin R. E., Proc. Natl. Acad. Sci. U.S.A. 98:4658-4663(2001); “CRISPR RNA maturation by trans-encoded small RNA and host factor RNase III.” Deltcheva E., Chylinski K., Sharma C. M., Gonzales K., Chao Y., Pirzada Z. A., Eckert M. R., Vogel J., Charpentier E., Nature 471:602-607(2011); and “A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.” Jinek M., Chylinski K., Fonfara I., Hauer M., Doudna J. A., Charpentier E. Science 337:816-821(2012), the entire contents of each of which are incorporated herein by reference.


Because RNA-programmable nucleases (e.g., Cas9) use RNA:DNA hybridization to target DNA cleavage sites, these proteins are able to be targeted, in principle, to any sequence specified by the guide RNA. Methods of using RNA-programmable nucleases, such as Cas9, for site-specific cleavage (e.g., to modify a genome) are known in the art (see e.g., Cong, L. et al. Multiplex genome engineering using CRISPR/Cas systems. Science 339, 819-823 (2013); Mali, P. et al. RNA-guided human genome engineering via Cas9. Science 339, 823-826 (2013); Hwang, W. Y. et al. Efficient genome editing in zebrafish using a CRISPR-Cas system. Nature biotechnology 31, 227-229 (2013); Jinek, M. et al. RNA-programmed genome editing in human cells. eLife 2, e00471 (2013); Dicarlo, J. E. et al. Genome engineering in Saccharomyces cerevisiae using CRISPR-Cas systems. Nucleic acids research (2013); Jiang, W. et al. RNA-guided editing of bacterial genomes using CRISPR-Cas systems. Nature biotechnology 31, 233-239 (2013); the entire contents of each of which are incorporated herein by reference).


The term “subject,” as used herein, refers to an individual organism, for example, an individual mammal. In some embodiments, the subject is a human. In some embodiments, the subject is a non-human mammal. In some embodiments, the subject is a non-human primate. In some embodiments, the subject is a rodent. In some embodiments, the subject is a sheep, a goat, a cattle, a cat, or a dog. In some embodiments, the subject is a vertebrate, an amphibian, a reptile, a fish, an insect, a fly, or a nematode. In some embodiments, the subject is a research animal. In some embodiments, the subject is genetically engineered, e.g., a genetically engineered non-human subject. The subject may be of either sex and at any stage of development.


The term “target site” refers to a sequence within a nucleic acid molecule that is deaminated by a deaminase or a fusion protein comprising a deaminase, (e.g., a dCas9-deaminase fusion protein provided herein).


The terms “treatment,” “treat,” and “treating,” refer to a clinical intervention aimed to reverse, alleviate, delay the onset of, or inhibit the progress of a disease or disorder, or one or more symptoms thereof, as described herein. As used herein, the terms “treatment,” “treat,” and “treating” refer to a clinical intervention aimed to reverse, alleviate, delay the onset of, or inhibit the progress of a disease or disorder, or one or more symptoms thereof, as described herein. In some embodiments, treatment may be administered after one or more symptoms have developed and/or after a disease has been diagnosed. In other embodiments, treatment may be administered in the absence of symptoms, e.g., to prevent or delay onset of a symptom or inhibit onset or progression of a disease. For example, treatment may be administered to a susceptible individual prior to the onset of symptoms (e.g., in light of a history of symptoms and/or in light of genetic or other susceptibility factors). Treatment may also be continued after symptoms have resolved, for example, to prevent or delay their recurrence.


The term “recombinant” as used herein in the context of proteins or nucleic acids refers to proteins or nucleic acids that do not occur in nature, but are the product of human engineering. For example, in some embodiments, a recombinant protein or nucleic acid molecule comprises an amino acid or nucleotide sequence that comprises at least one, at least two, at least three, at least four, at least five, at least six, or at least seven mutations as compared to any naturally occurring sequence.


The term “nucleobase editors (NBEs)” or “base editors (BEs),” as used herein, refers to the Cas9 fusion proteins described herein. In some embodiments, the fusion protein comprises a nuclease-inactive Cas9 (dCas9) fused to a deaminase. In some embodiments, the fusion protein comprises a Cas9 nickase fused to a deaminase. In some embodiments, the fusion protein comprises a nuclease-inactive Cas9 fused to a deaminase and further fused to a UGI domain. In some embodiments, the fusion protein comprises a Cas9 nickase fused to a deaminase and further fused to a UGI domain. In some embodiments, the dCas9 of the fusion protein comprises a D10A and a H840A mutation of SEQ ID NO: 10, or a corresponding mutation in any of SEQ ID NOs: 11-260, which inactivates nuclease activity of the Cas9 protein. In some embodiments, the fusion protein comprises a D10A mutation and comprises a histidine at residue 840 of SEQ ID NO: 10, or a corresponding mutation in any of SEQ ID NOs: 11-260, which renders Cas9 capable of cleaving only one strand of a nucleic acid duplex. An example of a Cas9 nickase is shown below in SEQ ID NO: 674. The terms “nucleobase editors (NBEs)” and “base editors (BEs)” may be used interchangeably.


The term “uracil glycosylase inhibitor” or “UGI,” as used herein, refers to a protein that is capable of inhibiting a uracil-DNA glycosylase base-excision repair enzyme.


The term “Cas9 nickase,” as used herein, refers to a Cas9 protein that is capable of cleaving only one strand of a duplexed nucleic acid molecule (e.g., a duplexed DNA molecule). In some embodiments, a Cas9 nickase comprises a D10A mutation and has a histidine at position H840 of SEQ ID NO: 10, or a corresponding mutation in any of SEQ ID NOs: 11-260. For example, a Cas9 nickase may comprise the amino acid sequence as set forth in SEQ ID NO: 674. Such a Cas9 nickase has an active HNH nuclease domain and is able to cleave the non-targeted strand of DNA, i.e., the strand bound by the gRNA. Further, such a Cas9 nickase has an inactive RuvC nuclease domain and is not able to cleave the targeted strand of the DNA, i.e., the strand where base editing is desired.


Exemplary Cas9 nickase (Cloning vector pPlatTET-gRNA2; Accession No. BAV54124).









(SEQ ID NO: 674)


MDKKYSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGAL





LFDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLE





ESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRL





IYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPINAS





GVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSN





FDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDIL





RVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKN





GYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRTFDNG





SIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGN





SRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPK





HSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTV





KQLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEEN





EDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWGRLS





RKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKEDIQKAQVS





GQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMAR





ENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYL





QNGRDMYVDQELDINRLSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKS





DNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERGGLSELDKAGFIK





RQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKD





FQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRK





MIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGE





IVWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIAR





KKDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSS





FEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGN





ELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISE





FSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKY





FDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD






DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS OF THE INVENTION

Some aspects of this disclosure provide fusion proteins that comprise a domain capable of binding to a nucleotide sequence (e.g., a Cas9, or a Cpf1 protein) and an enzyme domain, for example, a DNA-editing domain, such as, e.g., a deaminase domain. The deamination of a nucleobase by a deaminase can lead to a point mutation at the respective residue, which is referred to herein as nucleic acid editing. Fusion proteins comprising a Cas9 variant or domain and a DNA editing domain can thus be used for the targeted editing of nucleic acid sequences. Such fusion proteins are useful for targeted editing of DNA in vitro, e.g., for the generation of mutant cells or animals; for the introduction of targeted mutations, e.g., for the correction of genetic defects in cells ex vivo, e.g., in cells obtained from a subject that are subsequently re-introduced into the same or another subject; and for the introduction of targeted mutations, e.g., the correction of genetic defects or the introduction of deactivating mutations in disease-associated genes in a subject. Typically, the Cas9 domain of the fusion proteins described herein does not have any nuclease activity but instead is a Cas9 fragment or a dCas9 protein or domain. Methods for the use of Cas9 fusion proteins as described herein are also provided.


Cas9 Domains of Nucleobase Editors


Non-limiting, exemplary Cas9 domains are provided herein. The Cas9 domain may be a nuclease active Cas9 domain, a nucleasae inactive Cas9 domain, or a Cas9 nickase. In some embodiments, the Cas9 domain is a nuclease active domain. For example, the Cas9 domain may be a Cas9 domain that cuts both strands of a duplexed nucleic acid (e.g., both strands of a duplexed DNA molecule). In some embodiments, the Cas9 domain comprises any one of the amino acid sequences as set forth in SEQ ID NOs: 10-263. In some embodiments the Cas9 domain comprises an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to any one of the amino acid sequences set forth in SEQ ID NOs: 10-263. In some embodiments, the Cas9 domain comprises an amino acid sequence that has 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 21, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 or more or more mutations compared to any one of the amino acid sequences set forth in SEQ ID NOs: 10-263. In some embodiments, the Cas9 domain comprises an amino acid sequence that has at least 10, at least 15, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 150, at least 200, at least 250, at least 300, at least 350, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, at least 1000, at least 1100, or at least 1200 identical contiguous amino acid residues as compared to any one of the amino acid sequences set forth in SEQ ID NOs: 10-263.


In some embodiments, the Cas9 domain is a nuclease-inactive Cas9 domain (dCas9). For example, the dCas9 domain may bind to a duplexed nucleic acid molecule (e.g., via a gRNA molecule) without cleaving either strand of the duplexed nucleic acid molecule. In some embodiments, the nuclease-inactive dCas9 domain comprises a D10X mutation and a H840X mutation of the amino acid sequence set forth in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, wherein X is any amino acid change. In some embodiments, the nuclease-inactive dCas9 domain comprises a D10A mutation and a H840A mutation of the amino acid sequence set forth in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. As one example, a nuclease-inactive Cas9 domain comprises the amino acid sequence set forth in SEQ ID NO: 263 (Cloning vector pPlatTET-gRNA2, Accession No. BAV54124).









(SEQ ID NO: 263


MDKKYSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGAL





LFDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLE





ESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRL





IYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPINAS





GVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSN





FDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDIL





RVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKN





GYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRTFDNG





SIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGN





SRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPK





HSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTV





KQLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEEN





EDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWGRLS





RKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKEDIQKAQVS





GQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMAR





ENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYL





QNGRDMYVDQELDINRLSDYDVDAIVPQSFLKDDSIDNKVLTRSDKNRGKS





DNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERGGLSELDKAGFIK





RQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKD





FQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRK





MIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGE





IVWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIAR





KKDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSS





FEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGN





ELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISE





FSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKY





FDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD;







see e.g., Qi et al., Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell. 2013; 152(5):1173-83, the entire contents of which are incorporated herein by reference).


Additional suitable nuclease-inactive dCas9 domains will be apparent to those of skill in the art based on this disclosure and knowledge in the field, and are within the scope of this disclosure. Such additional exemplary suitable nuclease-inactive Cas9 domains include, but are not limited to, D10A/H840A, D10A/D839A/H840A, and D10A/D839A/H840A/N863A mutant domains (See, e.g., Prashant et al., CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nature Biotechnology. 2013; 31(9): 833-838, the entire contents of which are incorporated herein by reference). In some embodiments the dCas9 domain comprises an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to any one of the dCas9 domains provided herein. In some embodiments, the Cas9 domain comprises an amino acid sequences that has 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 21, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 or more or more mutations compared to any one of the amino acid sequences set forth in SEQ ID NOs: 10-263. In some embodiments, the Cas9 domain comprises an amino acid sequence that has at least 10, at least 15, at least 20, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 150, at least 200, at least 250, at least 300, at least 350, at least 400, at least 500, at least 600, at least 700, at least 800, at least 900, at least 1000, at least 1100, or at least 1200 identical contiguous amino acid residues as compared to any one of the amino acid sequences set forth in SEQ ID NOs: 10-263.


In some embodiments, the Cas9 domain is a Cas9 nickase. The Cas9 nickase may be a Cas9 protein that is capable of cleaving only one strand of a duplexed nucleic acid molecule (e.g., a duplexed DNA molecule). In some embodiments the Cas9 nickase cleaves the target strand of a duplexed nucleic acid molecule, meaning that the Cas9 nickase cleaves the strand that is base paired to (complementary to) a gRNA (e.g., an sgRNA) that is bound to the Cas9. In some embodiments, a Cas9 nickase comprises a D10A mutation and has a histidine at position 840 of SEQ ID NO: 10, or a mutation in any of SEQ ID NOs: 11-260. For example, a Cas9 nickase may comprise the amino acid sequence as set forth in SEQ ID NO: 674. In some embodiments the Cas9 nickase cleaves the non-target, non-base-edited strand of a duplexed nucleic acid molecule, meaning that the Cas9 nickase cleaves the strand that is not base paired to a gRNA (e.g., an sgRNA) that is bound to the Cas9. In some embodiments, a Cas9 nickase comprises an H840A mutation and has an aspartic acid residue at position 10 of SEQ ID NO: 10, or a corresponding mutation in any of SEQ ID NOs: 11-260. In some embodiments the Cas9 nickase comprises an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to any one of the Cas9 nickases provided herein. Additional suitable Cas9 nickases will be apparent to those of skill in the art based on this disclosure and knowledge in the field, and are within the scope of this disclosure.


Cas9 Domains with Reduced PAM Exclusivity


Some aspects of the disclosure provide Cas9 domains that have different PAM specificities. Typically, Cas9 proteins, such as Cas9 from S. pyogenes (spCas9), require a canonical NGG PAM sequence to bind a particular nucleic acid region. This may limit the ability to edit desired bases within a genome. In some embodiments, the base editing fusion proteins provided herein may need to be placed at a precise location, for example where a target base is placed within a 4 base region (e.g., a “deamination window”), which is approximately 15 bases upstream of the PAM. See Komor, A. C., et al., “Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage” Nature 533, 420-424 (2016), the entire contents of which are hereby incorporated by reference. Accordingly, in some embodiments, any of the fusion proteins provided herein may contain a Cas9 domain that is capable of binding a nucleotide sequence that does not contain a canonical (e.g., NGG) PAM sequence. Cas9 domains that bind to non-canonical PAM sequences have been described in the art and would be apparent to the skilled artisan. For example, Cas9 domains that bind non-canonical PAM sequences have been described in Kleinstiver, B. P., et al., “Engineered CRISPR-Cas9 nucleases with altered PAM specificities” Nature 523, 481-485 (2015); and Kleinstiver, B. P., et al., “Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition” Nature Biotechnology 33, 1293-1298 (2015); the entire contents of each are hereby incorporated by reference.


In some embodiments, the Cas9 domain is a Cas9 domain from Staphylococcus aureus (SaCas9). In some embodiments, the SaCas9 domain is a nuclease active SaCas9, a nuclease inactive SaCas9 (SaCas9d), or a SaCas9 nickase (SaCas9n). In some embodiments, the SaCas9 comprises the amino acid sequence SEQ ID NO: 4273. In some embodiments, the SaCas9 comprises a N579X mutation of SEQ ID NO: 4273, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, wherein X is any amino acid except for N. In some embodiments, the SaCas9 comprises a N579A mutation of SEQ ID NO: 4273, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the SaCas9 domain, the SaCas9d domain, or the SaCas9n domain can bind to a nucleic acid sequence having a non-canonical PAM. In some embodiments, the SaCas9 domain, the SaCas9d domain, or the SaCas9n domain can bind to a nucleic acid sequence having a NNGRRT PAM sequence. In some embodiments, the SaCas9 domain comprises one or more of a E781X, a N967X, and a R1014X mutation of SEQ ID NO: 4273, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, wherein X is any amino acid. In some embodiments, the SaCas9 domain comprises one or more of a E781K, a N967K, and a R1014H mutation of SEQ ID NO: 4273, or one or more corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the SaCas9 domain comprises a E781K, a N967K, or a R1014H mutation of SEQ ID NO: 4273, or corresponding mutations in any of the amino acid sequences provided in SEQ ID NOs: 11-260.


In some embodiments, the Cas9 domain of any of the fusion proteins provided herein comprises an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to any one of SEQ ID NOs: 4273-4275. In some embodiments, the Cas9 domain of any of the fusion proteins provided herein comprises the amino acid sequence of any one of SEQ ID NOs: 4273-4275. In some embodiments, the Cas9 domain of any of the fusion proteins provided herein consists of the amino acid sequence of any one of SEQ ID NOs: 4273-4275.









Exemplary SaCas9 sequence


(SEQ ID NO: 4273)


KRNYILGLDIGITSVGYGIIDYETRDVIDAGVRLFKEANVENNEGRRSKRG





ARRLKRRRRHRIQRVKKLLFDYNLLTDHSELSGINPYEARVKGLSQKLSEE





EFSAALLHLAKRRGVHNVNEVEEDTGNELSTKEQISRNSKALEEKYVAELQ





LERLKKDGEVRGSINRFKTSDYVKEAKQLLKVQKAYHQLDQSFIDTYIDLL





ETRRTYYEGPGEGSPFGWKDIKEWYEMLMGHCTYFPEELRSVKYAYNADLY





NALNDLNNLVITRDENEKLEYYEKFQIIENVFKQKKKPTLKQIAKEILVNE





EDIKGYRVTSTGKPEFTNLKVYHDIKDITARKEIIENAELLDQIAKILTIY





QSSEDIQEELTNLNSELTQEEIEQISNLKGYTGTHNLSLKAINLILDELWH





TNDNQIAIFNRLKLVPKKVDLSQQKEIPTTLVDDFILSPVVKRSFIQSIKV





INAIIKKYGLPNDIIIELAREKNSKDAQKMINEMQKRNRQTNERIEEIIRT





TGKENAKYLIEKIKLHDMQEGKCLYSLEAIPLEDLLNNPFNYEVDHIIPRS





VSFDNSFNNKVLVKQEENSKKGNRTPFQYLSSSDSKISYETFKKHILNLAK





GKGRISKTKKEYLLEERDINRFSVQKDFINRNLVDTRYATRGLMNLLRSYF





RVNNLDVKVKSINGGFTSFLRRKWKFKKERNKGYKHHAEDALIIANADFIF





KEWKKLDKAKKVMENQMFEEKQAESMPEIETEQEYKEIFITPHQIKHIKDF





KDYKYSHRVDKKPNRELINDTLYSTRKDDKGNTLIVNNLNGLYDKDNDKLK





KLINKSPEKLLMYHHDPQTYQKLKLIMEQYGDEKNPLYKYYEETGNYLTKY





SKKDNGPVIKKIKYYGNKLNAHLDITDDYPNSRNKVVKLSLKPYRFDVYLD





NGVYKFVTVKNLDVIKKENYYEVNSKCYEEAKKLKKISNQAEFIASFYNND





LIKINGELYRVIGVNNDLLNRIEVNMIDITYREYLENMNDKRPPRIIKTIA





SKTQSIKKYSTDILGNLYEVKSKKHPQIIKKG







Residue N579 of SEQ ID NO: 4273, which is underlined and in bold, may be mutated (e.g., to a A579) to yield a SaCas9 nickase.









Exemplary SaCas9n sequence


(SEQ ID NO: 4274)


KRNYILGLDIGITSVGYGIIDYETRDVIDAGVRLFKEANVENNEGRRSKR





GARRLKRRRRHRIQRVKKLLFDYNLLTDHSELSGINPYEARVKGLSQKLS





EEEFSAALLHLAKRRGVHNVNEVEEDTGNELSTKEQISRNSKALEEKYVA





ELQLERLKKDGEVRGSINRFKTSDYVKEAKQLLKVQKAYHQLDQSFIDTY





IDLLETRRTYYEGPGEGSPFGWKDIKEWYEMLMGHCTYFPEELRSVKYAY





NADLYNALNDLNNLVITRDENEKLEYYEKFQIIENVFKQKKKPTLKQIAK





EILVNEEDIKGYRVTSTGKPEFTNLKVYHDIKDITARKEIIENAELLDQI





AKILTIYQSSEDIQEELTNLNSELTQEEIEQISNLKGYTGTHNLSLKAIN





LILDELWHTNDNQIAIFNRLKLVPKKVDLSQQKEIPTTLVDDFILSPVVK





RSFIQSIKVINAIIKKYGLPNDIIIELAREKNSKDAQKMINEMQKRNRQT





NERIEEIIRTTGKENAKYLIEKIKLHDMQEGKCLYSLEAIPLEDLLNNPF





NYEVDHIIPRSVSFDNSFNNKVLVKQEEASKKGNRTPFQYLSSSDSKISY





ETFKKHILNLAKGKGRISKTKKEYLLEERDINRFSVQKDFINRNLVDTRY





ATRGLMNLLRSYFRVNNLDVKVKSINGGFTSFLRRKWKFKKERNKGYKHH





AEDALIIANADFIFKEWKKLDKAKKVMENQMFEEKQAESMPEIETEQEYK





EIFITPHQIKHIKDFKDYKYSHRVDKKPNRELINDTLYSTRKDDKGNTLI





VNNLNGLYDKDNDKLKKLINKSPEKLLMYHHDPQTYQKLKLIMEQYGDEK





NPLYKYYEETGNYLTKYSKKDNGPVIKKIKYYGNKLNAHLDITDDYPNSR





NKVVKLSLKPYRFDVYLDNGVYKFVTVKNLDVIKKENYYEVNSKCYEEAK





KLKKISNQAEFIASFYNNDLIKINGELYRVIGVNNDLLNRIEVNMIDITY





REYLENMNDKRPPRIIKTIASKTQSIKKYSTDILGNLYEVKSKKHPQIIK





KG.







Residue A579 of SEQ ID NO: xx, which can be mutated from N579 of SEQ ID NO: 4274 to yield a SaCas9 nickase, is underlined and in bold.









Exemplary SaKKH Cas9


(SEQ ID NO: 4275)


KRNYILGLDIGITSVGYGIIDYETRDVIDAGVRLFKEANVENNEGRRSKR





GARRLKRRRRHRIQRVKKLLFDYNLLTDHSELSGINPYEARVKGLSQKLS





EEEFSAALLHLAKRRGVHNVNEVEEDTGNELSTKEQISRNSKALEEKYVA





ELQLERLKKDGEVRGSINRFKTSDYVKEAKQLLKVQKAYHQLDQSFIDTY





IDLLETRRTYYEGPGEGSPFGWKDIKEWYEMLMGHCTYFPEELRSVKYAY





NADLYNALNDLNNLVITRDENEKLEYYEKFQIIENVFKQKKKPTLKQIAK





EILVNEEDIKGYRVTSTGKPEFTNLKVYHDIKDITARKEIIENAELLDQI





AKILTIYQSSEDIQEELTNLNSELTQEEIEQISNLKGYTGTHNLSLKAIN





LILDELWHTNDNQIAIFNRLKLVPKKVDLSQQKEIPTTLVDDFILSPVVK





RSFIQSIKVINAIIKKYGLPNDIIIELAREKNSKDAQKMINEMQKRNRQT





NERIEEIIRTTGKENAKYLIEKIKLHDMQEGKCLYSLEAIPLEDLLNNPF





NYEVDHIIPRSVSFDNSFNNKVLVKQEEASKKGNRTPFQYLSSSDSKISY





ETFKKHILNLAKGKGRISKTKKEYLLEERDINRFSVQKDFINRNLVDTRY





ATRGLMNLLRSYFRVNNLDVKVKSINGGFTSFLRRKWKFKKERNKGYKHH





AEDALIIANADFIFKEWKKLDKAKKVMENQMFEEKQAESMPEIETEQEYK





EIFITPHQIKHIKDFKDYKYSHRVDKKPNRKLINDTLYSTRKDDKGNTLI





VNNLNGLYDKDNDKLKKLINKSPEKLLMYHHDPQTYQKLKLIMEQYGDEK





NPLYKYYEETGNYLTKYSKKDNGPVIKKIKYYGNKLNAHLDITDDYPNSR





NKVVKLSLKPYRFDVYLDNGVYKFVTVKNLDVIKKENYYEVNSKCYEEAK





KLKKISNQAEFIASFYKNDLIKINGELYRVIGVNNDLLNRIEVNMIDITY





REYLENMNDKRPPHIIKTIASKTQSIKKYSTDILGNLYEVKSKKHPQIIK





KG.






Residue A579 of SEQ ID NO: 4275, which can be mutated from N579 of SEQ ID NO: 4275 to yield a SaCas9 nickase, is underlined and in bold. Residues K781, K967, and H1014 of SEQ ID NO: 4275, which can be mutated from E781, N967, and R1014 of SEQ ID NO: 4275 to yield a SaKKH Cas9 are underlined and in italics.


In some embodiments, the Cas9 domain is a Cas9 domain from Streptococcus pyogenes (SpCas9). In some embodiments, the SpCas9 domain is a nuclease active SpCas9, a nuclease inactive SpCas9 (SpCas9d), or a SpCas9 nickase (SpCas9n). In some embodiments, the SpCas9 comprises the amino acid sequence SEQ ID NO: 4276. In some embodiments, the SpCas9 comprises a D9X mutation of SEQ ID NO: 4276, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, wherein X is any amino acid except for D. In some embodiments, the SpCas9 comprises a D9A mutation of SEQ ID NO: 4276, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the SpCas9 domain, the SpCas9d domain, or the SpCas9n domain can bind to a nucleic acid sequence having a non-canonical PAM. In some embodiments, the SpCas9 domain, the SpCas9d domain, or the SpCas9n domain can bind to a nucleic acid sequence having a NGG, a NGA, or a NGCG PAM sequence. In some embodiments, the SpCas9 domain comprises one or more of a D1134X, a R1334X, and a T1336X mutation of SEQ ID NO: 4276, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, wherein X is any amino acid. In some embodiments, the SpCas9 domain comprises one or more of a D1134E, R1334Q, and T1336R mutation of SEQ ID NO: 4276, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the SpCas9 domain comprises a D1134E, a R1334Q, and a T1336R mutation of SEQ ID NO: 4276, or corresponding mutations in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the SpCas9 domain comprises one or more of a D1134X, a R1334X, and a T1336X mutation of SEQ ID NO: 4276, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, wherein X is any amino acid. In some embodiments, the SpCas9 domain comprises one or more of a D1134V, a R1334Q, and a T1336R mutation of SEQ ID NO: 4276, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the SpCas9 domain comprises a D1134V, a R1334Q, and a T1336R mutation of SEQ ID NO: 4276, or corresponding mutations in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the SpCas9 domain comprises one or more of a D1134X, a G1217X, a R1334X, and a T1336X mutation of SEQ ID NO: 4276, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, wherein X is any amino acid. In some embodiments, the SpCas9 domain comprises one or more of a D1134V, a G1217R, a R1334Q, and a T1336R mutation of SEQ ID NO: 4276, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the SpCas9 domain comprises a D1134V, a G1217R, a R1334Q, and a T1336R mutation of SEQ ID NO: 4276, or corresponding mutations in any of the amino acid sequences provided in SEQ ID NOs: 11-260.


In some embodiments, the Cas9 domain of any of the fusion proteins provided herein comprises an amino acid sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to any one of SEQ ID NOs: 4276-4280. In some embodiments, the Cas9 domain of any of the fusion proteins provided herein comprises the amino acid sequence of any one of SEQ ID NOs: 4276-4280. In some embodiments, the Cas9 domain of any of the fusion proteins provided herein consists of the amino acid sequence of any one of SEQ ID NOs: 4276-4280.









Exemplary SpCas9


(SEQ ID NO: 4276)


DKKYSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALL





FDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEE





SFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLI





YLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPINASG





VDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNF





DLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILR





VNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNG





YAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRTFDNGS





IPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNS





RFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKH





SLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVK





QLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENE





DILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWGRLSR





KLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKEDIQKAQVSG





QGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARE





NQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQ





NGRDMYVDQELDINRLSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKSD





NVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERGGLSELDKAGFIKR





QLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKDF





QFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKM





IAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEI





VWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARK





KDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSSF





EKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGNE





LALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISEF





SKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYF





DTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD





Exemplary SpCas9n


(SEQ ID NO: 4277)


DKKYSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALL





FDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEE





SFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLI





YLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPINASG





VDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNF





DLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILR





VNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNG





YAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRTFDNGS





IPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNS





RFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKH





SLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVK





QLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENE





DILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWGRLSR





KLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKEDIQKAQVSG





QGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARE





NQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQ





NGRDMYVDQELDINRLSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKSD





NVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERGGLSELDKAGFIKR





QLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKDF





QFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKM





IAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEI





VWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARK





KDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSSF





EKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGNE





LALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISEF





SKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYF





DTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD





Exemplary SpEQR Cas9


(SEQ ID NO: 4278)


DKKYSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALL





FDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEE





SFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLI





YLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPINASG





VDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNF





DLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILR





VNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNG





YAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRTFDNGS





IPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNS





RFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKH





SLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVK





QLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENE





DILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWGRLSR





KLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKEDIQKAQVSG





QGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARE





NQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQ





NGRDMYVDQELDINRLSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKSD





NVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERGGLSELDKAGFIKR





QLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKDF





QFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKM





IAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEI





VWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARK





KDWDPKKYGGFESPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSSF





EKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGNE





LALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISEF





SKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYF





DTTIDRKQYRSTKEVLDATLIHQSITGLYETRIDLSQLGGD







Residues E1134, Q1334, and R1336 of SEQ ID NO: 4278, which can be mutated from D1134, R1334, and T1336 of SEQ ID NO: 4278 to yield a SpEQR Cas9, are underlined and in bold.









Exemplary SpVQR Cas9


(SEQ ID NO: 4279)


DKKYSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGAL





LFDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRL





EESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADL





RLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPI





NASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPN





FKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAIL





LSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIF





FDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRK





QRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYY





VGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKN





LPNEKVLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDL





LFKTNRKVTVKQLKEDYFKKIECFDSVETSGVEDRFNASLGTYHDLLKII





KDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQL





KRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDS





LTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVM





GRHKPENIVIEMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPV





ENTQLQNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDHIVPQSFLKDDS





IDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLT





KAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR





EVKVITLKSKLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKY





PKLESEFVYGDYKVYDVRKMIAKSEQEIGKATAKYFFYSNIMNFFKTEIT





LANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLSMPQVNIVKKTEVQ





TGGFSKESILPKRNSDKLIARKKDWDPKKYGGFVSPTVAYSVLVVAKVEK





GKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKY





SLFELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPED





NEQKQLFVEQHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKP





IREQAENIIHLFTLTNLGAPAAFKYFDTTIDRKQYRSTKEVLDATLIHQS





ITGLYETRIDLSQLGGD







Residues V1134, Q1334, and R1336 of SEQ ID NO: 4279, which can be mutated from D1134, R1334, and T1336 of SEQ ID NO: 4279 to yield a SpVQR Cas9, are underlined and in bold.









Exemplary SpVRER Cas9


(SEQ ID NO: 4280)


DKKYSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGAL





LFDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRL





EESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADL





RLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPI





NASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPN





FKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAIL





LSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIF





FDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRK





QRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYY





VGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKN





LPNEKVLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDL





LFKTNRKVTVKQLKEDYFKKIECFDSVETSGVEDRFNASLGTYHDLLKII





KDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQL





KRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDS





LTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVM





GRHKPENIVIEMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPV





ENTQLQNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDHIVPQSFLKDDS





IDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLT





KAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR





EVKVITLKSKLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKY





PKLESEFVYGDYKVYDVRKMIAKSEQEIGKATAKYFFYSNIMNFFKTEIT





LANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLSMPQVNIVKKTEVQ





TGGFSKESILPKRNSDKLIARKKDWDPKKYGGFVSPTVAYSVLVVAKVEK





GKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKY





SLFELENGRKRMLASARELQKGNELALPSKYVNFLYLASHYEKLKGSPED





NEQKQLFVEQHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKP





IREQAENIIHLFTLTNLGAPAAFKYFDTTIDRKEYRSTKEVLDATLIHQS





ITGLYETRIDLSQLGGD







Residues V1134, R1217, Q1334, and R1336 of SEQ ID NO: 4280, which can be mutated from D1134, G1217, R1334, and T1336 of SEQ ID NO: 4280 to yield a SpVRER Cas9, are underlined and in bold.


The following are exemplary fusion proteins (e.g., base editing proteins) capable of binding to a nucleic acid sequence having a non-canonical (e.g., a non-NGG) PAM sequence:










Exemplary SaBE3 (rAPOBEC1-XTEN-SaCas9n-UGI-NLS)



(SEQ ID NO: 4281)



MSSETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSIWRHTSQNTNKHVE






VNFIEKFTTERYFCPNTRCSITWFLSWSPCGECSRAITEFLSRYPHVTLFIYIARLYHHADPR





NRQGLRDLISSGVTIQIMTEQESGYCWRNFVNYSPSNEAHWPRYPHLWVRLYVLELYCIILGL





PPCLNILRRKQPQLTFFTIALQSCHYQRLPPHILWATGLKSGSETPGTSESATPESKRNYILG






LDIGITSVGYGIIDYETRDVIDAGVRLFKEANVENNEGRRSKRGARRLKRRRRHRIQRVKKLL







FDYNLLTDHSELSGINPYEARVKGLSQKLSEEEFSAALLHLAKRRGVHNVNEVEEDTGNELST







KEQISRNSKALEEKYVAELQLERLKKDGEVRGSINRFKTSDYVKEAKQLLKVQKAYHQLDQSF







IDTYIDLLETRRTYYEGPGEGSPFGWKDIKEWYEMLMGHCTYFPEELRSVKYAYNADLYNALN







DLNNLVITRDENEKLEYYEKFQIIENVFKQKKKPTLKQIAKEILVNEEDIKGYRVTSTGKPEF







TNLKVYHDIKDITARKEIIENAELLDQIAKILTIYQSSEDIQEELTNLNSELTQEEIEQISNL







KGYTGTHNLSLKAINLILDELWHTNDNQIAIFNRLKLVPKKVDLSQQKEIPTTLVDDFILSPV







VKRSFIQSIKVINAIIKKYGLPNDIIIELAREKNSKDAQKMINEMQKRNRQTNERIEEIIRTT







GKENAKYLIEKIKLHDMQEGKCLYSLEAIPLEDLLNNPFNYEVDHIIPRSVSFDNSFNNKVLV







KQEEASKKGNRTPFQYLSSSDSKISYETFKKHILNLAKGKGRISKTKKEYLLEERDINRFSVQ







KDFINRNLVDTRYATRGLMNLLRSYFRVNNLDVKVKSINGGFTSFLRRKWKFKKERNKGYKHH







AEDALIIANADFIFKEWKKLDKAKKVMENQMFEEKQAESMPEIETEQEYKEIFITPHQIKHIK







DFKDYKYSHRVDKKPNRELINDTLYSTRKDDKGNTLIVNNLNGLYDKDNDKLKKLINKSPEKL







LMYHHDPQTYQKLKLIMEQYGDEKNPLYKYYEETGNYLTKYSKKDNGPVIKKIKYYGNKLNAH







LDITDDYPNSRNKVVKLSLKPYRFDVYLDNGVYKFVTVKNLDVIKKENYYEVNSKCYEEAKKL







KKISNQAEFIASFYNNDLIKINGELYRVIGVNNDLLNRIEVNMIDITYREYLENMNDKRPPRI







IKTIASKTQSIKKYSTDILGNLYEVKSKKHPQIIKKGSGGSTNLSDIIEKETGKQLVIQESIL






MLPEEVEEVIGNKPESDILVHTAYDESTDENVMLLTSDAPEYKPWALVIQDSNGENKIKMLSG





GSPKKKRKV





Exemplary SaKKH-BE3 (rAPOBEC1-XTEN-SaCas9n-UGI-NLS)


(SEQ ID NO: 4282)



MSSETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSIWRHTSQNTNKHVE






VNFIEKFTTERYFCPNTRCSITWFLSWSPCGECSRAITEFLSRYPHVTLFIYIARLYHHADPR





NRQGLRDLISSGVTIQIMTEQESGYCWRNFVNYSPSNEAHWPRYPHLWVRLYVLELYCIILGL





PPCLNILRRKQPQLTFFTIALQSCHYQRLPPHILWATGLKSGSETPGTSESATPESKRNYILG






LDIGITSVGYGIIDYETRDVIDAGVRLFKEANVENNEGRRSKRGARRLKRRRRHRIQRVKKLL







FDYNLLTDHSELSGINPYEARVKGLSQKLSEEEFSAALLHLAKRRGVHNVNEVEEDTGNELST







KEQISRNSKALEEKYVAELQLERLKKDGEVRGSINRFKTSDYVKEAKQLLKVQKAYHQLDQSF







IDTYIDLLETRRTYYEGPGEGSPFGWKDIKEWYEMLMGHCTYFPEELRSVKYAYNADLYNALN







DLNNLVITRDENEKLEYYEKFQIIENVFKQKKKPTLKQIAKEILVNEEDIKGYRVTSTGKPEF







TNLKVYHDIKDITARKEIIENAELLDQIAKILTIYQSSEDIQEELTNLNSELTQEEIEQISNL







KGYTGTHNLSLKAINLILDELWHTNDNQIAIFNRLKLVPKKVDLSQQKEIPTTLVDDFILSPV







VKRSFIQSIKVINAIIKKYGLPNDIIIELAREKNSKDAQKMINEMQKRNRQTNERIEEIIRTT







GKENAKYLIEKIKLHDMQEGKCLYSLEAIPLEDLLNNPFNYEVDHIIPRSVSFDNSFNNKVLV







KQEEASKKGNRTPFQYLSSSDSKISYETFKKHILNLAKGKGRISKTKKEYLLEERDINRFSVQ







KDFINRNLVDTRYATRGLMNLLRSYFRVNNLDVKVKSINGGFTSFLRRKWKFKKERNKGYKHH







AEDALIIANADFIFKEWKKLDKAKKVMENQMFEEKQAESMPEIETEQEYKEIFITPHQIKHIK







DFKDYKYSHRVDKKPNRKLINDTLYSTRKDDKGNTLIVNNLNGLYDKDNDKLKKLINKSPEKL







LMYHHDPQTYQKLKLIMEQYGDEKNPLYKYYEETGNYLTKYSKKDNGPVIKKIKYYGNKLNAH







LDITDDYPNSRNKVVKLSLKPYRFDVYLDNGVYKFVTVKNLDVIKKENYYEVNSKCYEEAKKL







KKISNQAEFIASFYKNDLIKINGELYRVIGVNNDLLNRIEVNMIDITYREYLENMNDKRPPHI







IKTIASKTQSIKKYSTDILGNLYEVKSKKHPQIIKKGSGGSTNLSDIIEKETGKQLVIQESIL






MLPEEVEEVIGNKPESDILVHTAYDESTDENVMLLTSDAPEYKPWALVIQDSNGENKIKMLSG





GSPKKKRKV





Exemplary EQR-BE3 (rAPOBEC1-XTEN-Cas9n-UGI-NLS)


(SEQ ID NO: 4283)



MSSETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSIWRHTSQNTNKHVE






VNFIEKFTTERYFCPNTRCSITWFLSWSPCGECSRAITEFLSRYPHVTLFIYIARLYHHADPR





NRQGLRDLISSGVTIQIMTEQESGYCWRNFVNYSPSNEAHWPRYPHLWVRLYVLELYCIILGL





PPCLNILRRKQPQLTFFTIALQSCHYQRLPPHILWATGLKSGSETPGTSESATPESDKKYSIG






LAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAEATRLKRTARRR







YTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAYHEKYPT







IYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFE







ENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNFDLAE







DAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIK







RYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGT







EELLVKLNREDLLRKQRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIP







YYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHS







LLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECF







DSVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKT







YAHLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDS







LTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMA







RENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQE







LDINRLSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAK







LITQRKFDNLTKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREV







KVITLKSKLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVY






DVRKMIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRD






FATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFESPTVAYS







VLVVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFE







LENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDE







IIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTI







DRKQYRSTKEVLDATLIHQSITGLYETRIDLSQLGGDSGGSTNLSDIIEKETGKQLVIQESIL






MLPEEVEEVIGNKPESDILVHTAYDESTDENVMLLTSDAPEYKPWALVIQDSNGENKIKMLSG





GSPKKKRKV





VQR-BE3 (rAPOBEC1-XTEN-Cas9n-UGI-NLS)


(SEQ ID NO: 4284)



MSSETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSIWRHTSQNTNKHVE






VNFIEKFTTERYFCPNTRCSITWFLSWSPCGECSRAITEFLSRYPHVTLFIYIARLYHHADPR





NRQGLRDLISSGVTIQIMTEQESGYCWRNFVNYSPSNEAHWPRYPHLWVRLYVLELYCIILGL





PPCLNILRRKQPQLTFFTIALQSCHYQRLPPHILWATGLKSGSETPGTSESATPESDKKYSIG






LAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAEATRLKRTARRR







YTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAYHEKYPT







IYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFE







ENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNFDLAE







DAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIK







RYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGT







EELLVKLNREDLLRKQRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIP







YYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHS







LLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECF







DSVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKT







YAHLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDS







LTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMA







RENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQE







LDINRLSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAK







LITQRKFDNLTKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREV







KVITLKSKLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVY







DVRKMIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRD







FATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFVSPTVAYS







VLVVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFE







LENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDE







IIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTI







DRKQYRSTKEVLDATLIHQSITGLYETRIDLSQLGGDSGGSTNLSDIIEKETGKQLVIQESIL






MLPEEVEEVIGNKPESDILVHTAYDESTDENVMLLTSDAPEYKPWALVIQDSNGENKIKMLSG





GSPKKKRKV





VRER-BE3 (rAPOBEC1-XTEN-Cas9n-UGI-NLS)


(SEQ ID NO: 4285)



MSSETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSIWRHTSQNTNKHVE






VNFIEKFTTERYFCPNTRCSITWFLSWSPCGECSRAITEFLSRYPHVTLFIYIARLYHHADPR





NRQGLRDLISSGVTIQIMTEQESGYCWRNFVNYSPSNEAHWPRYPHLWVRLYVLELYCIILGL





PPCLNILRRKQPQLTFFTIALQSCHYQRLPPHILWATGLKSGSETPGTSESATPESDKKYSIG






LAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAEATRLKRTARRR







YTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAYHEKYPT







IYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFE







ENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNFDLAE







DAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIK







RYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGT







EELLVKLNREDLLRKQRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIP







YYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHS







LLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECF







DSVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKT







YAHLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDS







LTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMA







RENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQE







LDINRLSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAK







LITQRKFDNLTKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREV







KVITLKSKLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVY







DVRKMIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRD







FATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGGFVSPTVAYS







VLVVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFE







LENGRKRMLASARELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDE







IIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTI







DRKEYRSTKEVLDATLIHQSITGLYETRIDLSQLGGDSGGSTNLSDIIEKETGKQLVIQESIL






MLPEEVEEVIGNKPESDILVHTAYDESTDENVMLLTSDAPEYKPWALVIQDSNGENKIKMLSG





GSPKKKRKV







High Fidelity Base Editors


Some aspects of the disclosure provide Cas9 fusion proteins (e.g., any of the fusion proteins provided herein) comprising a Cas9 domain that has high fidelity. Additional aspects of the disclosure provide Cas9 fusion proteins (e.g., any of the fusion proteins provided herein) comprising a Cas9 domain with decreased electrostatic interactions between the Cas9 domain and a sugar-phosphate backbone of a DNA, as compared to a wild-type Cas9 domain. In some embodiments, a Cas9 domain (e.g., a wild type Cas9 domain) comprises one or more mutations that decreases the association between the Cas9 domain and a sugar-phosphate backbone of a DNA. In some embodiments, any of the Cas9 fusion proteins provided herein comprise one or more of a N497X, a R661X, a Q695X, and/or a Q926X mutation of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, wherein X is any amino acid. In some embodiments, any of the Cas9 fusion proteins provided herein comprise one or more of a N497A, a R661A, a Q695A, and/or a Q926A mutation of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the Cas9 domain comprises a D10A mutation of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the Cas9 domain (e.g., of any of the fusion proteins provided herein) comprises the amino acid sequence as set forth in SEQ ID NO: 325. In some embodiments, the fusion protein comprises the amino acid sequence as set forth in SEQ ID NO: 285. Cas9 domains with high fidelity are known in the art and would be apparent to the skilled artisan. For example, Cas9 domains with high fidelity have been described in Kleinstiver, B. P., et al. “High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects.” Nature 529, 490-495 (2016); and Slaymaker, I. M., et al. “Rationally engineered Cas9 nucleases with improved specificity.” Science 351, 84-88 (2015); the entire contents of each are incorporated herein by reference.


It should be appreciated that the base editors provided herein, for example base editor 2 (BE2) or base editor 3 (BE3), may be converted into high fidelity base editors by modifying the Cas9 domain as described herein to generate high fidelity base editors, for example high fidelity base editor 2 (HF-BE2) or high fidelity base editor 3 (HF-BE3). In some embodiments, base editor 2 (BE2) comprises a deaminase domain, a dCas9, and a UGI domain. In some embodiments, base editor 3 (BE3) comprises a deaminase domain an nCas9 domain and a UGI domain.









Cas9 domain where mutations relative to Cas9


of SEQ ID NO: 10 are shown in bold and


underlines


(SEQ ID NO: 325)


DKKYSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGAL





LFDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRL





EESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADL





RLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPI





NASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPN





FKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAIL





LSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIF





FDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRK





QRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYY





VGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTAFDKN





LPNEKVLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDL





LFKTNRKVTVKQLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKII





KDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQL





KRRRYTGWGALSRKLINGIRDKQSGKTILDFLKSDGFANRNFMALIHDDS





LTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVM





GRHKPENIVIEMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPV





ENTQLQNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDHIVPQSFLKDDS





IDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLT





KAERGGLSELDKAGFIKRQLVETRAITKHVAQILDSRMNTKYDENDKLIR





EVKVITLKSKLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKY





PKLESEFVYGDYKVYDVRKMIAKSEQEIGKATAKYFFYSNIMNFFKTEIT





LANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLSMPQVNIVKKTEVQ





TGGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEK





GKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKY





SLFELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPED





NEQKQLFVEQHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKP





IREQAENIIHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLDATLIHQS





ITGLYETRIDLSQLGGD





HF-BE3


(SEQ ID NO: 285)


MSSETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSI





WRHTSQNTNKHVEVNFIEKFTTERYFCPNTRCSITWFLSWSPCGECSRAI





TEFLSRYPHVTLFIYIARLYHHADPRNRQGLRDLISSGVTIQIMTEQESG





YCWRNFVNYSPSNEAHWPRYPHLWVRLYVLELYCIILGLPPCLNILRRKQ





PQLTFFTIALQSCHYQRLPPHILWATGLKSGSETPGTSESATPESDKKYS





IGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSG





ETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFL





VEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYL





ALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPINASGV





DAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNF





DLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDIL





RVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSK





NGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRTFD





NGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLA





RGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTAFDKNLPNEK





VLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTN





RKVTVKQLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKIIKDKDF





LDNEENEDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRY





TGWGALSRKLINGIRDKQSGKTILDFLKSDGFANRNFMALIHDDSLTFKE





DIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKP





ENIVIEMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQL





QNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDHIVPQSFLKDDSIDNKV





LTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERG





GLSELDKAGFIKRQLVETRAITKHVAQILDSRMNTKYDENDKLIREVKVI





TLKSKLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLES





EFVYGDYKVYDVRKMIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGE





IRKRPLIETNGETGEIVWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFS





KESILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKK





LKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFEL





ENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQ





LFVEQHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQA





ENIIHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLDATLIHQSITGLY





ETRIDLSQLGGD







Cas9 Fusion Proteins


Any of the Cas9 domains (e.g., a nuclease active Cas9 protein, a nuclease-inactive dCas9 protein, or a Cas9 nickase protein) disclosed herein may be fused to a second protein, thus fusion proteins provided herein comprise a Cas9 domain as provided herein and a second protein, or a “fusion partner”. In some embodiments, the second protein is fused to the N-terminus of the Cas9 domain. However, in other embodiments, the second protein is fused to the C-terminus of the Cas9 domain. In some embodiments, the second protein that is fused to the Cas9 domain is a nucleic acid editing domain. In some embodiments, the Cas9 domain and the nucleic acid editing domain are fused via a linker, while in other embodiments the Cas9 domain and the nucleic acid editing domain are fused directly to one another. In some embodiments, the linker comprises (GGGS)n (SEQ ID NO: 265), (GGGGS)n (SEQ ID NO: 5), (G)n, (EAAAK)n (SEQ ID NO: 6), (GGS)n, (SGGS)n (SEQ ID NO: 4288), SGSETPGTSESATPES (SEQ ID NO: 7), or (XP)n motif, or a combination of any of these, wherein n is independently an integer between 1 and 30, and wherein X is any amino acid. In some embodiments, the linker comprises a (GGS)n motif, wherein n is 1, 3, or 7. In some embodiments, the linker comprises a (GGS)n motif, wherein n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15. In some embodiments, the linker comprises an amino acid sequence of SGSETPGTSESATPES (SEQ ID NO: 7),also referred to as the XTEN linker in the Examples). The length of the linker can influence the base to be edited, as illustrated in the Examples. For example, a linker of 3-amino-acid long (e.g., (GGS)1) may give a 2-5, 2-4, 2-3, 3-4 base editing window relative to the PAM sequence, while a 9-amino-acid linker (e.g., (GGS)3 (SEQ ID NO: 596)) may give a 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, 5-6 base editing window relative to the PAM sequence. A 16-amino-acid linker (e.g., the XTEN linker) may give a 2-7, 2-6, 2-5, 2-4, 2-3, 3-7, 3-6, 3-5, 3-4, 4-7, 4-6, 4-5, 5-7, 5-6, 6-7 base window relative to the PAM sequence with exceptionally strong activity, and a 21-amino-acid linker (e.g., (GGS)7 (SEQ ID NO: 597)) may give a 3-8, 3-7, 3-6, 3-5, 3-4, 4-8, 4-7, 4-6, 4-5, 5-8, 5-7, 5-6, 6-8, 6-7, 7-8 base editing window relative to the PAM sequence. The novel finding that varying linker length may allow the dCas9 fusion proteins of the disclosure to edit nucleobases different distances from the PAM sequence affords significant clinical importance, since a PAM sequence may be of varying distance to the disease-causing mutation to be corrected in a gene. It is to be understood that the linker lengths described as examples here are not meant to be limiting.


In some embodiments, the second protein comprises an enzymatic domain. In some embodiments, the enzymatic domain is a nucleic acid editing domain. Such a nucleic acid editing domain may be, without limitation, a nuclease, a nickase, a recombinase, a deaminase, a methyltransferase, a methylase, an acetylase, or an acetyltransferase. Non-limiting exemplary binding domains that may be used in accordance with this disclosure include transcriptional activator domains and transcriptional repressor domains.


Deaminase Domains


In some embodiments, second protein comprises a nucleic acid editing domain. In some embodiments, the nucleic acid editing domain can catalyze a C to U base change. In some embodiments, the nucleic acid editing domain is a deaminase domain. In some embodiments, the deaminase is a cytidine deaminase or a cytidine deaminase. In some embodiments, the deaminase is an apolipoprotein B mRNA-editing complex (APOBEC) family deaminase. In some embodiments, the deaminase is an APOBEC1 deaminase. In some embodiments, the deaminase is an APOBEC2 deaminase. In some embodiments, the deaminase is an APOBEC3 deaminase. In some embodiments, the deaminase is an APOBEC3A deaminase. In some embodiments, the deaminase is an APOBEC3B deaminase. In some embodiments, the deaminase is an APOBEC3C deaminase. In some embodiments, the deaminase is an APOBEC3D deaminase. In some embodiments, the deaminase is an APOBEC3E deaminase. In some embodiments, the deaminase is an APOBEC3F deaminase. In some embodiments, the deaminase is an APOBEC3G deaminase. In some embodiments, the deaminase is an APOBEC3H deaminase. In some embodiments, the deaminase is an APOBEC4 deaminase. In some embodiments, the deaminase is an activation-induced deaminase (AID). In some embodiments, the deaminase is a vertebrate deaminase. In some embodiments, the deaminase is an invertebrate deaminase. In some embodiments, the deaminase is a human, chimpanzee, gorilla, monkey, cow, dog, rat, or mouse deaminase. In some embodiments, the deaminase is a human deaminase. In some embodiments, the deaminase is a rat deaminase, e.g., rAPOBEC1. In some embodiments, the deaminase is a Petromyzon marinus cytidine deaminase 1 (pmCDA1). In some embodiments, the deminase is a human APOBEC3G (SEQ ID NO: 275). In some embodiments, the deaminase is a fragment of the human APOBEC3G (SEQ ID NO: 5740). In some embodiments, the deaminase is a human APOBEC3G variant comprising a D316R_D317R mutation (SEQ ID NO: 5739). In some embodiments, the deaminase is a frantment of the human APOBEC3G and comprising mutations corresponding to the D316R_D317R mutations in SEQ ID NO: 275 (SEQ ID NO: 5741).


In some embodiments, the nucleic acid editing domain is at least 80%, at least 85%, at least 90%, at least 92%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to the deaminase domain of any one of SEQ ID NOs: 266-284, 607-610, 5724-5736, or 5738-5741. In some embodiments, the nucleic acid editing domain comprises the amino acid sequence of any one of SEQ ID NOs: 266-284, 607-610, 5724-5736, or 5738-5741.


Deaminase Domains that Modulate the Editing Window of Base Editors


Some aspects of the disclosure are based on the recognition that modulating the deaminase domain catalytic activity of any of the fusion proteins provided herein, for example by making point mutations in the deaminase domain, affect the processivity of the fusion proteins (e.g., base editors). For example, mutations that reduce, but do not eliminate, the catalytic activity of a deaminase domain within a base editing fusion protein can make it less likely that the deaminase domain will catalyze the deamination of a residue adjacent to a target residue, thereby narrowing the deamination window. The ability to narrow the deamination window may prevent unwanted deamination of residues adjacent of specific target residues, which may decrease or prevent off-target effects.


In some embodiments, any of the fusion proteins provided herein comprise a deaminase domain (e.g., a cytidine deaminase domain) that has reduced catalytic deaminase activity. In some embodiments, any of the fusion proteins provided herein comprise a deaminase domain (e.g., a cytidine deaminase domain) that has a reduced catalytic deaminase activity as compared to an appropriate control. For example, the appropriate control may be the deaminase activity of the deaminase prior to introducing one or more mutations into the deaminase. In other embodiments, the appropriate control may be a wild-type deaminase. In some embodiments, the appropriate control is a wild-type apolipoprotein B mRNA-editing complex (APOBEC) family deaminase. In some embodiments, the appropriate control is an APOBEC1 deaminase, an APOBEC2 deaminase, an APOBEC3A deaminase, an APOBEC3B deaminase, an APOBEC3C deaminase, an APOBEC3D deaminase, an APOBEC3F deaminase, an APOBEC3G deaminase, or an APOBEC3H deaminase. In some embodiments, the appropriate control is an activation induced deaminase (AID). In some embodiments, the appropriate control is a cytidine deaminase 1 from Petromyzon marinus (pmCDA1). In some embodiments, the deaminase domain may be a deaminase domain that has at least 1%, at least 5%, at least 15%, at least 20%, at least 25%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, or at least 95% less catalytic deaminase activity as compared to an appropriate control.


In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising one or more mutations selected from the group consisting of H121X, H122X, R126X, R126X, R118X, W90X, W90X, and R132X of rAPOBEC1 (SEQ ID NO: 284), or one or more corresponding mutations in another APOBEC deaminase, wherein X is any amino acid. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising one or more mutations selected from the group consisting of H121R, H122R, R126A, R126E, R118A, W90A, W90Y, and R132E of rAPOBEC1 (SEQ ID NO: 284), or one or more corresponding mutations in another APOBEC deaminase.


In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising one or more mutations selected from the group consisting of D316X, D317X, R320X, R320X, R313X, W285X, W285X, R326X of hAPOBEC3G (SEQ ID NO: 275), or one or more corresponding mutations in another APOBEC deaminase, wherein X is any amino acid. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising one or more mutations selected from the group consisting of D316R, D317R, R320A, R320E, R313A, W285A, W285Y, R326E of hAPOBEC3G (SEQ ID NO: 275), or one or more corresponding mutations in another APOBEC deaminase.


In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a H121R and a H122R mutation of rAPOBEC1 (SEQ ID NO: 284), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a R126A mutation of rAPOBEC1 (SEQ ID NO: 284), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a R126E mutation of rAPOBEC1 (SEQ ID NO: 284), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a R118A mutation of rAPOBEC1 (SEQ ID NO: 284), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a W90A mutation of rAPOBEC1 (SEQ ID NO: 284), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a W90Y mutation of rAPOBEC1 (SEQ ID NO: 284), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a R132E mutation of rAPOBEC1 (SEQ ID NO: 284), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a W90Y and a R126E mutation of rAPOBEC1 (SEQ ID NO: 284), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a R126E and a R132E mutation of rAPOBEC1 (SEQ ID NO: 284), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a W90Y and a R132E mutation of rAPOBEC1 (SEQ ID NO: 284), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a W90Y, R126E, and R132E mutation of rAPOBEC1 (SEQ ID NO: 284), or one or more corresponding mutations in another APOBEC deaminase.


In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a D316R and a D317R mutation of hAPOBEC3G (SEQ ID NO: 275), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a R320A mutation of hAPOBEC3G (SEQ ID NO: 275), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a R320E mutation of hAPOBEC3G (SEQ ID NO: 275), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a R313A mutation of hAPOBEC3G (SEQ ID NO: 275), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a W285A mutation of hAPOBEC3G (SEQ ID NO: 275), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a W285Y mutation of hAPOBEC3G (SEQ ID NO: 275), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a R326E mutation of hAPOBEC3G (SEQ ID NO: 275), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a W285Y and a R320E mutation of hAPOBEC3G (SEQ ID NO: 275), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a R320E and a R326E mutation of hAPOBEC3G (SEQ ID NO: 275), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a W285Y and a R326E mutation of hAPOBEC3G (SEQ ID NO: 275), or one or more corresponding mutations in another APOBEC deaminase. In some embodiments, any of the fusion proteins provided herein comprise an APOBEC deaminase comprising a W285Y, R320E, and R326E mutation of hAPOBEC3G (SEQ ID NO: 275), or one or more corresponding mutations in another APOBEC deaminase.


Some aspects of this disclosure provide fusion proteins comprising (i) a nuclease-inactive Cas9 domain; and (ii) a nucleic acid editing domain. In some embodiments, a nuclease-inactive Cas9 domain (dCas9), comprises an amino acid sequence that is at least 80%, at least 85%, at least 90%, at least 92%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% identical to the amino acid sequence of a Cas9 as provided by any one of SEQ ID NOs: 10-263, and comprises mutations that inactivate the nuclease activity of Cas9. Mutations that render the nuclease domains of Cas9 inactive are well-known in the art. For example, the DNA cleavage domain of Cas9 is known to include two subdomains, the HNH nuclease subdomain and the RuvC1 subdomain. The HNH subdomain cleaves the strand complementary to the gRNA, whereas the RuvC1 subdomain cleaves the non-complementary strand. Mutations within these subdomains can silence the nuclease activity of Cas9. For example, the mutations D10A and H840A completely inactivate the nuclease activity of S. pyogenes Cas9 (Jinek et al., Science. 337:816-821(2012); Qi et al., Cell. 28; 152(5):1173-83 (2013)). In some embodiments, the dCas9 of this disclosure comprises a D10A mutation of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the dCas9 of this disclosure comprises a H840A mutation of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the dCas9 of this disclosure comprises both D10A and H840A mutations of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. In some embodiments, the Cas9 further comprises a histidine residue at position 840 of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. The presence of the catalytic residue H840 restores the acvitity of the Cas9 to cleave the non-edited strand containing a G opposite the targeted C. Restoration of H840 does not result in the cleavage of the target strand containing the C. In some embodiments, the dCas9 comprises an amino acid sequence of SEQ ID NO: 263. It is to be understood that other mutations that inactivate the nuclease domains of Cas9 may also be included in the dCas9 of this disclosure.


The Cas9 or dCas9 domains comprising the mutations disclosed herein, may be a full-length Cas9, or a fragment thereof. In some embodiments, proteins comprising Cas9, or fragments thereof, are referred to as “Cas9 variants.” A Cas9 variant shares homology to Cas9, or a fragment thereof. For example a Cas9 variant is at least about 70% identical, at least about 80% identical, at least about 90% identical, at least about 95% identical, at least about 96% identical, at least about 97% identical, at least about 98% identical, at least about 99% identical, at least about 99.5% identical, or at least about 99.9% to wild type Cas9. In some embodiments, the Cas9 variant comprises a fragment of Cas9 (e.g., a gRNA binding domain or a DNA-cleavage domain), such that the fragment is at least about 70% identical, at least about 80% identical, at least about 90% identical, at least about 95% identical, at least about 96% identical, at least about 97% identical, at least about 98% identical, at least about 99% identical, at least about 99.5% identical, or at least about 99.9% identical to the corresponding fragment of wild type Cas9, e.g., a Cas9 comprising the amino acid sequence of SEQ ID NO: 10.


Any of the Cas9 fusion proteins of this disclosure may further comprise a nucleic acid editing domain (e.g., an enzyme that is capable of modifying nucleic acid, such as a deaminase). In some embodiments, the nucleic acid editing domain is a DNA-editing domain. In some embodiments, the nucleic acid editing domain has deaminase activity. In some embodiments, the nucleic acid editing domain comprises or consists of a deaminase or deaminase domain. In some embodiments, the deaminase is a cytidine deaminase. In some embodiments, the deaminase is an apolipoprotein B mRNA-editing complex (APOBEC) family deaminase. In some embodiments, the deaminase is an APOBEC1 family deaminase. In some embodiments, the deaminase is an activation-induced cytidine deaminase (AID). Some nucleic-acid editing domains as well as Cas9 fusion proteins including such domains are described in detail herein. Additional suitable nucleic acid editing domains will be apparent to the skilled artisan based on this disclosure and knowledge in the field.


Some aspects of the disclosure provide a fusion protein comprising a Cas9 domain fused to a nucleic acid editing domain, wherein the nucleic acid editing domain is fused to the N-terminus of the Cas9 domain. In some embodiments, the Cas9 domain and the nucleic acid editing-editing domain are fused via a linker. In some embodiments, the linker comprises a (GGGS)n (SEQ ID NO: 265), a (GGGGS)n (SEQ ID NO: 5), a (G)n, an (EAAAK)n (SEQ ID NO: 6), a (GGS)n, (SGGS)n (SEQ ID NO: 4288), an SGSETPGTSESATPES (SEQ ID NO: 7) motif (see, e.g., Guilinger J P, Thompson D B, Liu D R. Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification. Nat. Biotechnol. 2014; 32(6): 577-82; the entire contents are incorporated herein by reference), or an (XP)n motif, or a combination of any of these, wherein n is independently an integer between 1 and 30. In some embodiments, n is independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30, or, if more than one linker or more than one linker motif is present, any combination thereof. In some embodiments, the linker comprises a (GGS)n motif, wherein n is 1,2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15. In some embodiments, the linker comprises a (GGS)n motif, wherein n is 1, 3, or 7. In some embodiments, the linker comprises the amino acid sequence SGSETPGTSESATPES (SEQ ID NO: 7). Additional suitable linker motifs and linker configurations will be apparent to those of skill in the art. In some embodiments, suitable linker motifs and configurations include those described in Chen et al., Fusion protein linkers: property, design and functionality. Adv Drug Deliv Rev. 2013; 65(10):1357-69, the entire contents of which are incorporated herein by reference. Additional suitable linker sequences will be apparent to those of skill in the art based on the instant disclosure. In some embodiments, the general architecture of exemplary Cas9 fusion proteins provided herein comprises the structure:

    • [NH2]-[nucleic acid editing domain]-[Cas9]-[COOH] or
    • [NH2]-[nucleic acid editing domain]-[linker]-[Cas9]-[COOH],


      wherein NH2 is the N-terminus of the fusion protein, and COOH is the C-terminus of the fusion protein.


The fusion proteins of the present disclosure may comprise one or more additional features. For example, in some embodiments, the fusion protein comprises a nuclear localization sequence (NLS). In some embodiments, the NLS of the fusion protein is localized between the nucleic acid editing domain and the Cas9 domain. In some embodiments, the NLS of the fusion protein is localized C-terminal to the Cas9 domain.


Other exemplary features that may be present are localization sequences, such as cytoplasmic localization sequences, export sequences, such as nuclear export sequences, or other localization sequences, as well as sequence tags that are useful for solubilization, purification, or detection of the fusion proteins. Suitable protein tags provided herein include, but are not limited to, biotin carboxylase carrier protein (BCCP) tags, myc-tags, calmodulin-tags, FLAG-tags, hemagglutinin (HA)-tags, polyhistidine tags, also referred to as histidine tags or His-tags, maltose binding protein (MBP)-tags, nus-tags, glutathione-S-transferase (GST)-tags, green fluorescent protein (GFP)-tags, thioredoxin-tags, S-tags, Softags (e.g., Softag 1, Softag 3), strep-tags, biotin ligase tags, FlAsH tags, V5 tags, and SBP-tags. Additional suitable sequences will be apparent to those of skill in the art. In some embodiments, the fusion protein comprises one or more His tags.


In some embodiments, the nucleic acid editing domain is a deaminase. For example, in some embodiments, the general architecture of exemplary Cas9 fusion proteins with a deaminase domain comprises the structure:

    • [NH2]-[NLS]-[deaminase]-[Cas9]-[COOH],
    • [NH2]-[Cas9]-[deaminase]-[COOH],
    • [NH2]-[deaminase]-[Cas9]-[COOH], or
    • [NH2]-[deaminase]-[Cas9]-[NLS]-[COOH]


      wherein NLS is a nuclear localization sequence, NH2 is the N-terminus of the fusion protein, and COOH is the C-terminus of the fusion protein. Nuclear localization sequences are known in the art and would be apparent to the skilled artisan. For example, NLS sequences are described in Plank et al., PCT/EP2000/011690, the contents of which are incorporated herein by reference for their disclosure of exemplary nuclear localization sequences. In some embodiments, a NLS comprises the amino acid sequence PKKKRKV (SEQ ID NO: 741) or MDSLLMNRRKFLYQFKNVRWAKGRRETYLC (SEQ ID NO: 742). In some embodiments, a linker is inserted between the Cas9 and the deaminase. In some embodiments, the NLS is located C-terminal of the Cas9 domain. In some embodiments, the NLS is located N-terminal of the Cas9 domain. In some embodiments, the NLS is located between the deaminase and the Cas9 domain. In some embodiments, the NLS is located N-terminal of the deaminase domain. In some embodiments, the NLS is located C-terminal of the deaminase domain.


One exemplary suitable type of nucleic acid editing domain is a cytidine deaminase, for example, of the APOBEC family. The apolipoprotein B mRNA-editing complex (APOBEC) family of cytidine deaminase enzymes encompasses eleven proteins that serve to initiate mutagenesis in a controlled and beneficial manner.29 One family member, activation-induced cytidine deaminase (AID), is responsible for the maturation of antibodies by converting cytosines in ssDNA to uracils in a transcription-dependent, strand-biased fashion.30 The apolipoprotein B editing complex 3 (APOBEC3) enzyme provides protection to human cells against a certain HIV-1 strain via the deamination of cytosines in reverse-transcribed viral ssDNA.31 These proteins all require a Zn2+-coordinating motif (His-X-Glu-X23-26-Pro-Cys-X2-4-Cys; SEQ ID NO: 598) and bound water molecule for catalytic activity. The Glu residue acts to activate the water molecule to a zinc hydroxide for nucleophilic attack in the deamination reaction. Each family member preferentially deaminates at its own particular “hotspot”, ranging from WRC (W is A or T, R is A or G) for hAID, to TTC for hAPOBEC3F.32 A recent crystal structure of the catalytic domain of APOBEC3G revealed a secondary structure comprised of a five-stranded β-sheet core flanked by six α-helices, which is believed to be conserved across the entire family.33 The active center loops have been shown to be responsible for both ssDNA binding and in determining “hotspot” identity.34 Overexpression of these enzymes has been linked to genomic instability and cancer, thus highlighting the importance of sequence-specific targeting.35


Some aspects of this disclosure relate to the recognition that the activity of cytidine deaminase enzymes such as APOBEC enzymes can be directed to a specific site in genomic DNA. Without wishing to be bound by any particular theory, advantages of using Cas9 as a recognition agent include (1) the sequence specificity of Cas9 can be easily altered by simply changing the sgRNA sequence; and (2) Cas9 binds to its target sequence by denaturing the dsDNA, resulting in a stretch of DNA that is single-stranded and therefore a viable substrate for the deaminase. It should be understood that other catalytic domains, or catalytic domains from other deaminases, can also be used to generate fusion proteins with Cas9, and that the disclosure is not limited in this regard.


Some aspects of this disclosure are based on the recognition that Cas9:deaminase fusion proteins can efficiently deaminate nucleotides at positions 3-11 according to the numbering scheme in FIG. 3. In view of the results provided herein regarding the nucleotides that can be targeted by Cas9:deaminase fusion proteins, a person of skill in the art will be able to design suitable guide RNAs to target the fusion proteins to a target sequence that comprises a nucleotide to be deaminated.


In some embodiments, the deaminase domain and the Cas9 domain are fused to each other via a linker. Various linker lengths and flexibilities between the deaminase domain (e.g., AID) and the Cas9 domain can be employed (e.g., ranging from very flexible linkers of the form (GGGGS)n (SEQ ID NO: 5), (GGS)n, and (G)n to more rigid linkers of the form (EAAAK)n (SEQ ID NO: 6), (SGGS)n (SEQ ID NO: 4288), SGSETPGTSESATPES (SEQ ID NO: 7) (see, e.g., Guilinger J P, Thompson D B, Liu D R. Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification. Nat. Biotechnol. 2014; 32(6): 577-82; the entire contents are incorporated herein by reference) and (XP)n)36 in order to achieve the optimal length for deaminase activity for the specific application. In some embodiments, the linker comprises a (GGS)n motif, wherein n is 1, 3, or 7. In some embodiments, the linker comprises a (an SGSETPGTSESATPES (SEQ ID NO: 7) motif.


Some exemplary suitable nucleic-acid editing domains, e.g., deaminases and deaminase domains, that can be fused to Cas9 domains according to aspects of this disclosure are provided below. It should be understood that, in some embodiments, the active domain of the respective sequence can be used, e.g., the domain without a localizing signal (nuclear localization sequence, without nuclear export signal, cytoplasmic localizing signal).










Human AID:



(SEQ ID NO: 266)




MDSLLMNRRKFLYQFKNVRWAKGRRETYLCYVVKRRDSATSFSLDFGYLRNKNGCHVELLFLR







YISDWDLDPGRCYRVTWFTSWSPCYDCARHVADFLRGNPNLSLRIFTARLYFCEDRKAEPEGL





RRLHRAGVQIAIMTFKDYFYCWNTFVENHERTFKAWEGLHENSVRLSRQLRRILLPLYEVDDL






RDAFRTLGL



(underline: nuclear localization sequence;


double underline: nuclear export signal)





Mouse AID:


(SEQ ID NO: 267)




MDSLLMKQKKFLYHFKNVRWAKGRHETYLCYVVKRRDSATSCSLDFGHLRNKSGCHVELLFLR







YISDWDLDPGRCYRVTWFTSWSPCYDCARHVAEFLRWNPNLSLRIFTARLYFCEDRKAEPEGL





RRLHRAGVQIGIMTFKDYFYCWNTFVENRERTFKAWEGLHENSVRLTRQLRRILLPLYEVDDL






RDAFRMLGF



(underline: nuclear localization sequence;


double underline: nuclear export signal)





Dog AID:


(SEQ ID NO: 268)




MDSLLMKQRKFLYHFKNVRWAKGRHETYLCYVVKRRDSATSFSLDFGHLRNKSGCHVELLFLR







YISDWDLDPGRCYRVTWFTSWSPCYDCARHVADFLRGYPNLSLRIFAARLYFCEDRKAEPEGL





RRLHRAGVQIAIMTFKDYFYCWNTFVENREKTFKAWEGLHENSVRLSRQLRRILLPLYEVDDL






RDAFRTLGL



(underline: nuclear localization sequence;


double underline: nuclear export signal)





Bovine AID:


(SEQ ID NO: 269)




MDSLLKKQRQFLYQFKNVRWAKGRHETYLCYVVKRRDSPTSFSLDFGHLRNKAGCHVELLFLR







YISDWDLDPGRCYRVTWFTSWSPCYDCARHVADFLRGYPNLSLRIFTARLYFCDKERKAEPEG





LRRLHRAGVQIAIMTFKDYFYCWNTFVENHERTFKAWEGLHENSVRLSRQLRRILLPLYEVDD






LRDAFRTLGL



(underline: nuclear localization sequence;


double underline: nuclear export signal)





Rat AID


(SEQ ID NO: 5725)




MAVGSKPKAALVGPHWERERIWCFLCSTGLGTQQTGQTSRWLRPAATQDPVSPPRSLLMKQRK







FLYHFKNVRWAKGRHETYLCYVVKRRDSATSFSLDFGYLRNKSGCHVELLFLRYISDWDLDPG





RCYRVTWFTSWSPCYDCARHVADFLRGNPNLSLRIFTARLTGWGALPAGLMSPARPSDYFYCW





NTFVENHERTFKAWEGLHENSVRLSRRLRRILLPLYEVDDLRDAFRTLGL


(underline: nuclear localization sequence;


double underline: nuclear export signal)





Mouse APOBEC-3:


(SEQ ID NO: 270)



MGPFCLGCSHRKCYSPIRNLISQETFKFHFKNLGYAKGRKDTFLCYEVTRKDCDSPVSLHHGV






FKNKDNIHAEICFLYWFHDKVLKVLSPREEFKITWYMSWSPCFECAEQIVRFLATHHNLSLDI





FSSRLYNVQDPETQQNLCRLVQEGAQVAAMDLYEFKKCWKKFVDNGGRRFRPWKRLLTNFRYQ





DSKLQEILRPCYIPVPSSSSSTLSNICLTKGLPETRFCVEGRRMDPLSEEEFYSQFYNQRVKH





LCYYHRMKPYLCYQLEQFNGQAPLKGCLLSEKGKQHAEILFLDKIRSMELSQVTITCYLTWSP






CPNCAWQLAAFKRDRPDLILHIYTSRLYFHWKRPFQKGLCSLWQSGILVDVMDLPQFTDCWTN






FVNPKRPFWPWKGLEIISRRTQRRLRRIKESWGLQDLVNDFGNLQLGPPMS


(italic: nucleic acid editing domain)





Rat APOBEC-3:


(SEQ ID NO: 271)



MGPFCLGCSHRKCYSPIRNLISQETFKFHFKNLRYAIDRKDTFLCYEVTRKDCDSPVSLHHGV






FKNKDNIHAEICFLYWFHDKVLKVLSPREEFKITWYMSWSPCFECAEQVLRFLATHHNLSLDI





FSSRLYNIRDPENQQNLCRLVQEGAQVAAMDLYEFKKCWKKFVDNGGRRFRPWKKLLTNFRYQ





DSKLQEILRPCYIPVPSSSSSTLSNICLTKGLPETRFCVERRRVHLLSEEEFYSQFYNQRVKH





LCYYHGVKPYLCYQLEQFNGQAPLKGCLLSEKGKQHAEILFLDKIRSMELSQVIITCYLTWSP






CPNCAWQLAAFKRDRPDLILHIYTSRLYFHWKRPFQKGLCSLWQSGILVDVMDLPQFTDCWTN






FVNPKRPFWPWKGLEIISRRTQRRLHRIKESWGLQDLVNDFGNLQLGPPMS


(italic: nucleic acid editing domain)





Rhesus macaque APOBEC-3G:


(SEQ ID NO: 272)




MVEPMDPRTFVSNFNNRPILSGLNTVWLCCEVKTKDPSGPPLDAKIFQGKVYSKAKYHPEM
RF








LRWFHKWRQLHHDQEYKVTWYVSWSPCTRCANSVATFLAKDPKVTLTIFVARLYYFWKPDYQQ






ALRILCQKRGGPHATMKIMNYNEFQDCWNKFVDGRGKPFKPRNNLPKHYTLLQATLGELLRHL





MDPGTFTSNFNNKPWVSGQHETYLCYKVERLHNDTWVPLNQHRGFLRNQAPNIHGFPKGRHAE






LCFLDLIPFWKLDGQQYRVTCFTSWSPCFSCAQEMAKFISNNEHVSLCIFAARIYDDQGRYQE






GLRALHRDGAKIAMMNYSEFEYCWDTFVDRQGRPFQPWDGLDEHSQALSGRLRAI


(italic: nucleic acid editing domain; underline:


cytoplasmic localization signal)





Chimpanzee APOBEC-3G:


(SEQ ID NO: 273)




MKPHFRNPVERMYQDTFSDNFYNRPILSHRNTVWLCYEVKTKGPSRPPLDAKIFRGQVYSKLK







YHPEMRFFHWFSKWRKLHRDQEYEVIWYISWSPCTKCTRDVATFLAEDPKVTLTIFVARLYYF





WDPDYQEALRSLCQKRDGPRATMKIMNYDEFQHCWSKFVYSQRELFEPWNNLPKYYILLHIML





GEILRHSMDPPTFTSNFNNELWVRGRHETYLCYEVERLHNDTWVLLNQRRGFLCNQAPHKHGF





LEGRHAELCFLDVIPFWKLDLHQDYRVTCFTSWSPCFSCAQEMAKFISNNKHVSLCIFAARIY





DDQGRCQEGLRTLAKAGAKISIMTYSEFKHCWDTFVDHQGCPFQPWDGLEEHSQALSGRLRAI





LQNQGN


(italic: nucleic acid editing domain; underline:


cytoplasmic localization signal)





Green monkey APOBEC-3G:


(SEQ ID NO: 274)




MNPQIRNMVEQMEPDIFVYYFNNRPILSGRNTVWLCYEVKTKDPSGPPLDANIFQGKLYPEAK







DHPEMKFLHWFRKWRQLHRDQEYEVTWYVSWSPCTRCANSVATFLAEDPKVTLTIFVARLYYF





WKPDYQQALRILCQERGGPHATMKIMNYNEFQHCWNEFVDGQGKPFKPRKNLPKHYTLLHATL





GELLRHVMDPGTFTSNFNNKPWVSGQRETYLCYKVERSHNDTWVLLNQHRGFLRNQAPDRHGF





PKGRHAELCFLDLIPFWKLDDQQYRVTCFTSWSPCFSCAQKMAKFISNNKHVSLCIFAARIYD





DQGRCQEGLRTLHRDGAKIAVMNYSEFEYCWDTFVDRQGRPFQPWDGLDEHSQALSGRLRAI


(italic: nucleic acid editing domain; underline:


cytoplasmic localization signal)





Human APOBEC-3G:


(SEQ ID NO: 275)




MKPHFRNTVERMYRDTFSYNFYNRPILSRRNTVWLCYEVKTKGPSRPPLDAKIFRGQVYSELK







YHPEMRFFHWFSKWRKLHRDQEYEVTWYISWSPCTKCTRDMATFLAEDPKVTLTIFVARLYYF





WDPDYQEALRSLCQKRDGPRATMKIMNYDEFQHCWSKFVYSQRELFEPWNNLPKYYILLHIML





GEILRHSMDPPTFTFNFNNEPWVRGRHETYLCYEVERMHNDTWVLLNQRRGFLCNQAPHKHGF





LEGRHAELCFLDVIPFWKLDLDQDYRVTCFTSWSPCFSCAQEMAKFISKNKHVSLCIFTARIY





DDQGRCQEGLRTLAEAGAKISIMTYSEFKHCWDTFVDHQGCPFQPWDGLDEHSQDLSGRLRAI





LQNQEN


(italic: nucleic acid editing domain; underline:


cytoplasmic localization signal)





Human APOBEC-3F:


(SEQ ID NO: 276)



MKPHFRNTVERMYRDTFSYNFYNRPILSRRNTVWLCYEVKTKGPSRPRLDAKIFRGQ






VYSQPEHHAEMCFLSWFCGNQLPAYKCFQITWFVSWTPCPDCVAKLAEFLAEHPNVTL





TISAARLYYYWERDYRRALCRLSQAGARVKIMDDEEFAYCWENFVYSEGQPFMPW





YKFDDNYAFLHRTLKEILRNPMEAMYPHIFYFHFKNLRKAYGRNESWLCFTMEVVK





HHSPVSWKRGVFRNQVDPETHCHAERCFLSWFCDDILSPNTNYEVTWYTSWSPCPECA





GEVAEFLARHSNVNLTIFTARLYYFWDTDYQEGLRSLSQEGASVEIMGYKDFKYCW





ENFVYNDDEPFKPWKGLKYNFLFLDSKLQEILE


(italic: nucleic acid editing domain)





Human APOBEC-3B:


(SEQ ID NO: 277)



MNPQIRNPMERMYRDTFYDNFENEPILYGRSYTWLCYEVKIKRGRSNLLWDTGVFR






GQVYFKPQYHAEMCFLSWFCGNQLPAYKCFQITWFVSWTPCPDCVAKLAEFLSEHPN





VTLTISAARLYYYWERDYRRALCRLSQAGARVTIMDYEEFAYCWENFVYNEGQQF





MPWYKFDENYAFLHRTLKEILRYLMDPDTFTFNFNNDPLVLRRRQTYLCYEVERLD





NGTWVLMDQHMGFLCNEAKNLLCGFYGRHAELRFLDLVPSLQLDPAQIYRVTWFISWS






PCFSWGCAGEVRAFLQENTHVRLRIFAARIYDYDPLYKEALQMLRDAGAQVSIMTY






DEFEYCWDTFVYRQGCPFQPWDGLEEHSQALSGRLRAILQNQGN


(italic: nucleic acid editing domain)





Rat APOBEC-3B:


(SEQ ID NO: 5729)



MQPQGLGPNAGMGPVCLGCSHRRPYSPIRNPLKKLYQQTFYFHFKNVRYAWGRKN






NFLCYEVNGMDCALPVPLRQGVFRKQGHIHAELCFIYWFHDKVLRVLSPMEEFKVT





WYMSWSPCSKCAEQVARFLAAHRNLSLAIFSSRLYYYLRNPNYQQKLCRLIQEGVH





VAAMDLPEFKKCWNKFVDNDGQPFRPWMRLRINFSFYDCKLQEIFSRMNLLREDVF





YLQFNNSHRVKPVQNRYYRRKSYLCYQLERANGQEPLKGYLLYKKGEQHVEILFLE





KMRSMELSQVRITCYLTWSPCPNCARQLAAFKKDHPDLILRIYTSRLYFYWRKKFQK





GLCTLWRSGIHVDVMDLPQFADCWTNFVNPQRPFRPWNELEKNSWRIQRRLRRIKE





SWGL





Bovine APOBEC-3B:


(SEQ ID NO: 5730)



DGWEVAFRSGTVLKAGVLGVSMTEGWAGSGHPGQGACVWTPGTRNTMNLLREVL






FKQQFGNQPRVPAPYYRRKTYLCYQLKQRNDLTLDRGCFRNKKQRHAEIRFIDKINS





LDLNPSQSYKIICYITWSPCPNCANELVNFITRNNHLKLEIFASRLYFHWIKSFKMGLQ





DLQNAGISVAVMTHTEFEDCWEQFVDNQSRPFQPWDKLEQYSASIRRRLQRILTAPI





Chimpanzee APOBEC -3B:


(SEQ ID NO: 5731)



MNPQIRNPMEWMYQRTFYYNFENEPILYGRSYTWLCYEVKIRRGHSNLLWDTGVFR






GQMYSQPEHHAEMCFLSWFCGNQLSAYKCFQITWFVSWTPCPDCVAKLAKFLAEHP





NVTLTISAARLYYYWERDYRRALCRLSQAGARVKIMDDEEFAYCWENFVYNEGQPF





MPWYKFDDNYAFLHRTLKEIIRHLMDPDTFTFNFNNDPLVLRRHQTYLCYEVERLD





NGTWVLMDQHMGFLCNEAKNLLCGFYGRHAELRFLDLVPSLQLDPAQIYRVTWFIS





WSPCFSWGCAGQVRAFLQENTHVRLRIFAARIYDYDPLYKEALQMLRDAGAQVSIM





TYDEFEYCWDTFVYRQGCPFQPWDGLEEHSQALSGRLRAILQVRASSLCMVPHRPPP





PPQSPGPCLPLCSEPPLGSLLPTGRPAPSLPFLLTASFSFPPPASLPPLPSLSLSPGHLPVP





SFHSLTSCSIQPPCSSRIRETEGWASVSKEGRDLG





Human APOBEC-3C:


(SEQ ID NO: 278)



MNPQIRNPMKAMYPGTFYFQFKNLWEANDRNETWLCFTVEGIKRRSVVSWKTGVF






RNQVDSETHCHAERCFLSWFCDDILSPNTKYQVIWYTSWSPCPDCAGEVAEFLARHSN





VNLTIFTARLYYFQYPCYQEGLRSLSQEGVAVEIMDYEDFKYCWENFVYNDNEPFKP





WKGLKTNFRLLKRRLRESLQ


(italic: nucleic acid editing domain)





Gorilla APOB EC3C


(SEQ ID NO: 5726)



MNPQIRNPMKAMYPGTFYFQFKNLWEANDRNETWLCFTVEGIKRRSVVSWKTGVF






RNQVDSETHCHAERCFLSWFCDDILSPNTNYQVIWYTSWSPCPECAGEVAEFLARHSN





VNLTIFTARLYYFQDTDYQEGLRSLSQEGVAVKIMDYKDFKYCWENFVYNDDEPFK





PWKGLKYNFRFLKRRLQEILE


(italic: nucleic acid editing domain)





Human APOBEC-3A:


(SEQ ID NO: 279)



MEASPASGPRHLMDPHIFTSNFNNGIGRHKTYLCYEVERLDNGTSVKMDQHRGFLH






NQAKNLLCGFYGRHAELRFLDLVPSLQLDPAQIYRVTWFISWSPCFSWGCAGEVRAFLQ





ENTHVRLRIFAARIYDYDPLYKEALQMLRDAGAQVSIMTYDEFKHCWDTFVDHQGC





PFQPWDGLDEHSQALSGRLRAILQNQGN


(italic: nucleic acid editing domain)





Rhesus macaque APOBEC-3A:


(SEQ ID NO: 5727)



MDGSPASRPRHLMDPNTFTFNFNNDLSVRGRHQTYLCYEVERLDNGTWVPMDERR






GFLCNKAKNVPCGDYGCHVELRFLCEVPSWQLDPAQTYRVTWFISWSPCFRRGCAGQ





VRVFLQENKHVRLRIFAARIYDYDPLYQEALRTLRDAGAQVSIMTYEEFKHCWDTF





VDRQGRPFQPWDGLDEHSQALSGRLRAILQNQGN


(italic: nucleic acid editing domain)





Bovine APOBEC-3A:


(SEQ ID NO: 5728)



MDEYTFTENFNNQGWPSKTYLCYEMERLDGDATIPLDEYKGFVRNKGLDQPEKPCH







AELYFLGKIHSWNLDRNQHYRLTCFISWSPCYDCAQKLTTFLKENHHISLHILASRIYTH






NRFGCHQSGLCELQAAGARITIMTFEDFKHCWETFVDHKGKPFQPWEGLNVKSQAL





CTELQAILKTQQN


(italic: nucleic acid editing domain)





Human APOBEC-3H:


(SEQ ID NO: 280)



MALLTAETFRLQFNNKRRLRRPYYPRKALLCYQLTPQNGSTPTRGYFENKKKCHAEI







CFINEIKSMGLDETQCYQVTCYLTWSPCSSCAWELVDFIKAHDHLNLGIFASRLYYHWC






KPQQKGLRLLCGSQVPVEVMGFPKFADCWENFVDHEKPLSFNPYKMLEELDKNSRA





IKRRLERIKIPGVRAQGRYMDILCDAEV


(italic: nucleic acid editing domain)





Rhesus macaque APOBEC-3H:


(SEQ ID NO: 5732)



MALLTAKTFSLQFNNKRRVNKPYYPRKALLCYQLTPQNGSTPTRGHLKNKKKDHAE






IRFINKIKSMGLDETQCYQVTCYLTWSPCPSCAGELVDFIKAHRHLNLRIFASRLYYH





WRPNYQEGLLLLCGSQVPVEVMGLPEFTDCWENFVDHKEPPSFNPSEKLEELDKNS





QAIKRRLERIKSRSVDVLENGLRSLQLGPVTPSSSIRNSR





Human APOBEC-3D:


(SEQ ID NO: 281)



MNPQIRNPMERMYRDTFYDNFENEPILYGRSYTWLCYEVKIKRGRSNLLWDTGVFR






GPVLPKRQSNHRQEVYFRFENHAEMCFLSWFCGNRLPANRRFQITWFVSWNPCLPCVV





KVTKFLAEHPNVTLTISAARLYYYRDRDWRWVLLRLHKAGARVKIMDYEDFAYCW





ENFVCNEGQPFMPWYKFDDNYASLHRTLKEILRNPMEAMYPHIFYFHFKNLLKACG





RNESWLCFTMEVTKHHSAVFRKRGVFRNQVDPETHCHAERCFLSWFCDDILSPNTNY






EVTWYTSWSPCPECAGEVAEFLARHSNVNLTIFTARLCYFWDTDYQEGLCSLSQEGAS






VKIMGYKDFVSCWKNFVYSDDEPFKPWKGLQTNFRLLKRRLREILQ


(italic: nucleic acid editing domain)





Human APOBEC-1:


(SEQ ID NO: 282)


MTSEKGPSTGDPTLRRRIEPWEFDVFYDPRELRKEACLLYEIKWGMSRKIWRSSGKN





TTNHVEVNFIKKFTSERDFHPSMSCSITWFLSWSPCWECSQAIREFLSRHPGVTLVIYV





ARLFWHMDQQNRQGLRDLVNSGVTIQIMRASEYYHCWRNFVNYPPGDEAHWPQYP





PLWMMLYALELHCIILSLPPCLKISRRWQNHLTFFRLHLQNCHYQTIPPHILLATGLIH





PSVAWR





Mouse APOBEC-1:


(SEQ ID NO: 283)



MSSETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSVWRHTSQN






TSNHVEVNFLEKFTTERYFRPNTRCSITWFLSWSPCGECSRAITEFLSRHPYVTLFIYIA





RLYHHTDQRNRQGLRDLISSGVTIQIMTEQEYCYCWRNFVNYPPSNEAYWPRYPHL





WVKLYVLELYCIILGLPPCLKILRRKQPQLTFFTITLQTCHYQRIPPHLLWATGLK





Rat APOBEC-1:


(SEQ ID NO: 284)



MSSETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSIWRHTSQNT






NKHVEVNFIEKFTTERYFCPNTRCSITWFLSWSPCGECSRAITEFLSRYPHVTLFIYIAR





LYHHADPRNRQGLRDLISSGVTIQIMTEQESGYCWRNFVNYSPSNEAHWPRYPHLW





VRLYVLELYCIILGLPPCLNILRRKQPQLTFFTIALQSCHYQRLPPHILWATGLK





Human APOBEC-2:


(SEQ ID NO: 5733)



MAQKEEAAVATEAASQNGEDLENLDDPEKLKELIELPPFEIVTGERLPANFFKFQFRN






VEYSSGRNKTFLCYVVEAQGKGGQVQASRGYLEDEHAAAHAEEAFFNTILPAFDPALR





YNVTWYVSSSPCAACADRIIKTLSKTKNLRLLILVGRLFMWEEPEIQAALKKLKEAG





CKLRIMKPQDFEYVWQNFVEQEEGESKAFQPWEDIQENFLYYEEKLADILK





Mouse APOBEC-2:


(SEQ ID NO: 5734)



MAQKEEAAEAAAPASQNGDDLENLEDPEKLKELIDLPPFEIVTGVRLPVNFFKFQFR






NVEYSSGRNKTFLCYVVEVQSKGGQAQATQGYLEDEHAGAHAEEAFFNTILPAFDP





ALKYNVTWYVSSSPCAACADRILKTLSKTKNLRLLILVSRLFMWEEPEVQAALKKLK





EAGCKLRIMKPQDFEYIWQNFVEQEEGESKAFEPWEDIQENFLYYEEKLADILK





Rat APOBEC-2:


(SEQ ID NO: 5735)



MAQKEEAAEAAAPASQNGDDLENLEDPEKLKELIDLPPFEIVTGVRLPVNFFKFQFR






NVEYSSGRNKTFLCYVVEAQSKGGQVQATQGYLEDEHAGAHAEEAFFNTILPAFDP





ALKYNVTWYVSSSPCAACADRILKTLSKTKNLRLLILVSRLFMWEEPEVQAALKKLK





EAGCKLRIMKPQDFEYLWQNFVEQEEGESKAFEPWEDIQENFLYYEEKLADILK





Bovine APOBEC-2:


(SEQ ID NO: 5736)



MAQKEEAAAAAEPASQNGEEVENLEDPEKLKELIELPPFEIVTGERLPAHYFKFQFRN






VEYSSGRNKTFLCYVVEAQSKGGQVQASRGYLEDEHATNHAEEAFFNSIMPTFDPALR





YMVTWYVSSSPCAACADRIVKTLNKTKNLRLLILVGRLFMWEEPEIQAALRKLKEA





GCRLRIMKPQDFEYIWQNFVEQEEGESKAFEPWEDIQENFLYYEEKLADILK





Petromyzon marinus CDA1 (pmCDA1)


(SEQ ID NO: 5738)



MTDAEYVRIHEKLDIYTFKKQFFNNKKSVSHRCYVLFELKRRGERRACFWGYAVNK






PQSGTERGIHAEIFSIRKVEEYLRDNPGQFTINWYSSWSPCADCAEKILEWYNQELRG





NGHTLKIWACKLYYEKNARNQIGLWNLRDNGVGLNVMVSEHYQCCRKIFIQSSHNQ





LNENRWLEKTLKRAEKRRSELSIMIQVKILHTTKSPAV





Human APOBEC3G D316R_D317R


(SEQ ID NO: 5739)



MKPHFRNTVERMYRDTFSYNFYNRPILSRRNTVWLCYEVKTKGPSRPPLDAKIFRGQ






VYSELKYHPEMRFFHWFSKWRKLHRDQEYEVTWYISWSPCTKCTRDMATFLAEDP





KVTLTIFVARLYYFWDPDYQEALRSLCQKRDGPRATMKIMNYDEFQHCWSKFVYSQ





RELFEPWNNLPKYYILLHIMLGEILRHSMDPPTFTFNFNNEPWVRGRHETYLCYEVER





MHNDTWVLLNQRRGFLCNQAPHKHGFLEGRHAELCFLDVIPFWKLDLDQDYRVTC





FTSWSPCFSCAQEMAKFISKNKHVSLCIFTARIYRRQGRCQEGLRTLAEAGAKISIMT





YSEFKHCWDTFVDHQGCPFQPWDGLDEHSQDLSGRLRAILQNQEN





Human APOBEC3G chain A


(SEQ ID NO: 5740)



MDPPTFTFNFNNEPWVRGRHETYLCYEVERMHNDTWVLLNQRRGFLCNQAPHKHG






FLEGRHAELCFLDVIPFWKLDLDQDYRVTCFTSWSPCFSCAQEMAKFISKNKHVSLCI





FTARIYDDQGRCQEGLRTLAEAGAKISIMTYSEFKHCWDTFVDHQGCPFQPWDGLD





EHSQDLSGRLRAILQ





Human APOBEC3G chain A D120R_D121R


(SEQ ID NO: 5741)



MDPPTFTFNFNNEPWVRGRHETYLCYEVERMHNDTWVLLNQRRGFLCNQAPHKHG






FLEGRHAELCFLDVIPFWKLDLDQDYRVTCFTSWSPCFSCAQEMAKFISKNKHVSLCI





FTARIYRRQGRCQEGLRTLAEAGAKISIMTYSEFKHCWDTFVDHQGCPFQPWDGLDE





HSQDLSGRLRAILQ






In some embodiments, fusion proteins as provided herein comprise the full-length amino acid of a nucleic acid editing enzyme, e.g., one of the sequences provided above. In other embodiments, however, fusion proteins as provided herein do not comprise a full-length sequence of a nucleic acid editing enzyme, but only a fragment thereof. For example, in some embodiments, a fusion protein provided herein comprises a Cas9 domain and a fragment of a nucleic acid editing enzyme, e.g., wherein the fragment comprises a nucleic acid editing domain. Exemplary amino acid sequences of nucleic acid editing domains are shown in the sequences above as italicized letters, and additional suitable sequences of such domains will be apparent to those of skill in the art.


Additional suitable nucleic-acid editing enzyme sequences, e.g., deaminase enzyme and domain sequences, that can be used according to aspects of this invention, e.g., that can be fused to a nuclease-inactive Cas9 domain, will be apparent to those of skill in the art based on this disclosure. In some embodiments, such additional enzyme sequences include deaminase enzyme or deaminase domain sequences that are at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% similar to the sequences provided herein. Additional suitable Cas9 domains, variants, and sequences will also be apparent to those of skill in the art. Examples of such additional suitable Cas9 domains include, but are not limited to, D10A, D10A/D839A/H840A, and D10A/D839A/H840A/N863A mutant domains (See, e.g., Prashant et al., CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nature Biotechnology. 2013; 31(9): 833-838 the entire contents of which are incorporated herein by reference). In some embodiments, the Cas9 comprises a histidine residue at position 840 of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260. The presence of the catalytic residue H840 restores the acvitity of the Cas9 to cleave the non-edited strand containing a G opposite the targeted C. Restoration of H840 does not result in the cleavage of the target strand containing the C.


Additional suitable strategies for generating fusion proteins comprising a Cas9 domain and a deaminase domain will be apparent to those of skill in the art based on this disclosure in combination with the general knowledge in the art. Suitable strategies for generating fusion proteins according to aspects of this disclosure using linkers or without the use of linkers will also be apparent to those of skill in the art in view of the instant disclosure and the knowledge in the art. For example, Gilbert et al., CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell. 2013; 154(2):442-51, showed that C-terminal fusions of Cas9 with VP64 using 2 NLS's as a linker (SPKKKRKVEAS, SEQ ID NO: 599), can be employed for transcriptional activation. Mali et al., CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering. Nat Biotechnol. 2013; 31(9):833-8, reported that C-terminal fusions with VP64 without linker can be employed for transcriptional activation. And Maeder et al., CRISPR RNA-guided activation of endogenous human genes. Nat Methods. 2013; 10: 977-979, reported that C-terminal fusions with VP64 using a Gly4Ser (SEQ ID NO: 5) linker can be used as transcriptional activators. Recently, dCas9—FokI nuclease fusions have successfully been generated and exhibit improved enzymatic specificity as compared to the parental Cas9 enzyme (In Guilinger J P, Thompson D B, Liu D R. Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification. Nat. Biotechnol. 2014; 32(6): 577-82, and in Tsai S Q, Wyvekens N, Khayter C, Foden J A, Thapar V, Reyon D, Goodwin M J, Aryee M J, Joung J K. Dimeric CRISPR RNA-guided FokI nucleases for highly specific genome editing. Nat Biotechnol. 2014; 32(6):569-76. PMID: 24770325 a SGSETPGTSESATPES (SEQ ID NO: 7) or a GGGGS (SEQ ID NO: 5) linker was used in FokI-dCas9 fusion proteins, respectively).


Some aspects of this disclosure provide fusion proteins comprising (i) a Cas9 enzyme or domain (e.g., a first protein); and (ii) a nucleic acid-editing enzyme or domain (e.g., a second protein). In some aspects, the fusion proteins provided herein further include (iii) a programmable DNA-binding protein, for example, a zinc-finger domain, a TALE, or a second Cas9 protein (e.g., a third protein). Without wishing to be bound by any particular theory, fusing a programmable DNA-binding protein (e.g., a second Cas9 protein) to a fusion protein comprising (i) a Cas9 enzyme or domain (e.g., a first protein); and (ii) a nucleic acid-editing enzyme or domain (e.g., a second protein) may be useful for improving specificity of the fusion protein to a target nucleic acid sequence, or for improving specificity or binding affinity of the fusion protein to bind target nucleic acid sequence that does not contain a canonical PAM (NGG) sequence. In some embodiments, the third protein is a Cas9 protein (e.g, a second Cas9 protein). In some embodiments, the third protein is any of the Cas9 proteins provided herein. In some embodiments, the third protein is fused to the fusion protein N-terminal to the Cas9 protein (e.g., the first protein). In some embodiments, the third protein is fused to the fusion protein C-terminal to the Cas9 protein (e.g., the first protein). In some embodiments, the Cas9 domain (e.g., the first protein) and the third protein (e.g., a second Cas9 protein) are fused via a linker (e.g., a second linker). In some embodiments, the linker comprises a (GGGGS)n (SEQ ID NO: 5), a (G)n, an (EAAAK)n (SEQ ID NO: 6), a (GGS)n, (SGGS)n (SEQ ID NO: 4288), an SGSETPGTSESATPES (SEQ ID NO: 7), or an (XP)n motif, or a combination of any of these, wherein n is independently an integer between 1 and 30. In some embodiments, the general architecture of exemplary Cas9 fusion proteins provided herein comprises the structure:

    • [NH2]-[nucleic acid-editing enzyme or domain]-[Cas9]-[third protein]-[COOH];
    • [NH2]-[third protein]-[Cas9]-[nucleic acid-editing enzyme or domain]-[COOH];
    • [NH2]-[Cas9]-[nucleic acid-editing enzyme or domain]-[third protein]-[COOH];
    • [NH2]-[third protein]-[nucleic acid-editing enzyme or domain]-[Cas9]-[COOH];
    • [NH2]-[UGI]-[nucleic acid-editing enzyme or domain]-[Cas9]-[third protein]-[COOH];
    • [NH2]-[UGI]-[third protein]-[Cas9]-[nucleic acid-editing enzyme or domain]-[COOH];
    • [NH2]-[UGI]-[Cas9]-[nucleic acid-editing enzyme or domain]-[third protein]-[COOH];
    • [NH2]-[UGI]-[third protein]-[nucleic acid-editing enzyme or domain]-[Cas9]-[COOH];
    • [NH2]-[nucleic acid-editing enzyme or domain]-[Cas9]-[third protein]-[UGI]-[COOH];
    • [NH2]-[third protein]-[Cas9]-[nucleic acid-editing enzyme or domain]-[UGI]-[COOH];
    • [NH2]-[Cas9]-[nucleic acid-editing enzyme or domain]-[third protein]-[UGI]-[COOH]; or
    • [NH2]-[third protein]-[nucleic acid-editing enzyme or domain]-[Cas9]-[UGI]-[COOH];


      wherein NH2 is the N-terminus of the fusion protein, and COOH is the C-terminus of the fusion protein. In some embodiments, the “]-[” used in the general architecture above indicates the presence of an optional linker sequence. In other examples, the general architecture of exemplary Cas9 fusion proteins provided herein comprises the structure:
    • [NH2]-[nucleic acid-editing enzyme or domain]-[Cas9]-[second Cas9 protein]-[COOH];
    • [NH2]-[second Cas9 protein]-[Cas9]-[nucleic acid-editing enzyme or domain]-[COOH];
    • [NH2]-[Cas9]-[nucleic acid-editing enzyme or domain]-[second Cas9 protein]-[COOH];
    • [NH2]-[second Cas9 protein]-[nucleic acid-editing enzyme or domain]-[Cas9]-[COOH];
    • [NH2]-[UGI]-[nucleic acid-editing enzyme or domain]-[Cas9]-[second Cas9 protein]-[COOH],
    • [NH2]-[UGI]-[second Cas9 protein]-[Cas9]-[nucleic acid-editing enzyme or domain]-[COOH];
    • [NH2]-[UGI]-[Cas9]-[nucleic acid-editing enzyme or domain]-[second Cas9 protein]-[COOH];
    • [NH2]-[UGI]-[second Cas9 protein]-[nucleic acid-editing enzyme or domain]-[Cas9]-[COOH];
    • [NH2]-[nucleic acid-editing enzyme or domain]-[Cas9]-[second Cas9 protein]-[UGI]-[COOH];
    • [NH2]-[second Cas9 protein]-[Cas9]-[nucleic acid-editing enzyme or domain]-[UGI]-[COOH];
    • [NH2]-[Cas9]-[nucleic acid-editing enzyme or domain]-[second Cas9 protein]-[UGI]-[COOH]; or
    • [NH2]-[second Cas9 protein]-[nucleic acid-editing enzyme or domain]-[Cas9]-[UGI]-[COOH];


      wherein NH2 is the N-terminus of the fusion protein, and COOH is the C-terminus of the fusion protein. In some embodiments, the “]-[” used in the general architecture above indicates the presence of an optional linker sequence. In some embodiments, the second Cas9 is a dCas9 protein. In some examples, the general architecture of exemplary Cas9 fusion proteins provided herein comprises a structure as shown in FIG. 3. It should be appreciated that any of the proteins provided in any of the general architectures of exemplary Cas9 fusion proteins may be connected by one or more of the linkers provided herein. In some embodiments, the linkers are the same. In some embodiments, the linkers are different. In some embodiments, one or more of the proteins provided in any of the general architectures of exemplary Cas9 fusion proteins are not fused via a linker. In some embodiments, the fusion proteins further comprise a nuclear targeting sequence, for example a nuclear localization sequence. In some embodiments, fusion proteins provided herein further comprise a nuclear localization sequence (NLS). In some embodiments, the NLS is fused to the N-terminus of the fusion protein. In some embodiments, the NLS is fused to the C-terminus of the fusion protein. In some embodiments, the NLS is fused to the N-terminus of the third protein. In some embodiments, the NLS is fused to the C-terminus of the third protein. In some embodiments, the NLS is fused to the N-terminus of the Cas9 protein. In some embodiments, the NLS is fused to the C-terminus of the Cas9 protein. In some embodiments, the NLS is fused to the N-terminus of the nucleic acid-editing enzyme or domain. In some embodiments, the NLS is fused to the C-terminus of the nucleic acid-editing enzyme or domain. In some embodiments, the NLS is fused to the N-terminus of the UGI protein. In some embodiments, the NLS is fused to the C-terminus of the UGI protein. In some embodiments, the NLS is fused to the fusion protein via one or more linkers. In some embodiments, the NLS is fused to the fusion protein without a linker


      Uracil Glycosylase Inhibitor Fusion Proteins


Some aspects of the disclosure relate to fusion proteins that comprise a uracil glycosylase inhibitor (UGI) domain. In some embodiments, any of the fusion proteins provided herein that comprise a Cas9 domain (e.g., a nuclease active Cas9 domain, a nuclease inactive dCas9 domain, or a Cas9 nickase) may be further fused to a UGI domain either directly or via a linker. Some aspects of this disclosure provide deaminase-dCas9 fusion proteins, deaminase-nuclease active Cas9 fusion proteins and deaminase-Cas9 nickase fusion proteins with increased nucleobase editing efficiency. Without wishing to be bound by any particular theory, cellular DNA-repair response to the presence of U:G heteroduplex DNA may be responsible for the decrease in nucleobase editing efficiency in cells. For example, uracil DNA glycosylase (UDG) catalyzes removal of U from DNA in cells, which may initiate base excision repair, with reversion of the U:G pair to a C:G pair as the most common outcome. As demonstrated in the Examples below, Uracil DNA Glycosylase Inhibitor (UGI) may inhibit human UDG activity. Thus, this disclosure contemplates a fusion protein comprising dCas9-nucleic acid editing domain futher fused to a UGI domain. This disclosure also contemplates a fusion protein comprising a Cas9 nickase-nucleic acid editing domain further fused to a UGI domain. It should be understood that the use of a UGI domain may increase the editing efficiency of a nucleic acid editing domain that is capable of catalyzing a C to U change. For example, fusion proteins comprising a UGI domain may be more efficient in deaminating C residues. In some embodiments, the fusion protein comprises the structure:

    • [deaminase]-[optional linker sequence]-[dCas9]-[optional linker sequence]-[UGI];
    • [deaminase]-[optional linker sequence]-[UGI]-[optional linker sequence]-[dCas9];
    • [UGI]-[optional linker sequence]-[deaminase]-[optional linker sequence]-[dCas9];
    • [UGI]-[optional linker sequence]-[dCas9]-[optional linker sequence]-[deaminase];
    • [dCas9]-[optional linker sequence]-[deaminase]-[optional linker sequence]-[UGI]; or
    • [dCas9]-[optional linker sequence]-[UGI]-[optional linker sequence]-[deaminase].


In other embodiments, the fusion protein comprises the structure:

    • [deaminase]-[optional linker sequence]-[Cas9 nickase]-[optional linker sequence]-[UGI];
    • [deaminase]-[optional linker sequence]-[UGI]-[optional linker sequence]-[Cas9 nickase];
    • [UGI]-[optional linker sequence]-[deaminase]-[optional linker sequence]-[Cas9 nickase];
    • [UGI]-[optional linker sequence]-[Cas9 nickase]-[optional linker sequence]-[deaminase];
    • [Cas9 nickase]-[optional linker sequence]-[deaminase]-[optional linker sequence]-[UGI]; or
    • [Cas9 nickase]-[optional linker sequence]-[UGI]-[optional linker sequence]-[deaminase].


In some embodiments, the fusion proteins provided herein do not comprise a linker sequence. In some embodiments, one or both of the optional linker sequences are present.


In some embodiments, the “-” used in the general architecture above indicates the presence of an optional linker sequence. In some embodiments, the fusion proteins comprising a UGI further comprise a nuclear targeting sequence, for example a nuclear localization sequence. In some embodiments, fusion proteins provided herein further comprise a nuclear localization sequence (NLS). In some embodiments, the NLS is fused to the N-terminus of the fusion protein. In some embodiments, the NLS is fused to the C-terminus of the fusion protein. In some embodiments, the NLS is fused to the N-terminus of the UGI protein. In some embodiments, the NLS is fused to the C-terminus of the UGI protein. In some embodiments, the NLS is fused to the N-terminus of the Cas9 protein. In some embodiments, the NLS is fused to the C-terminus of the Cas9 protein. In some embodiments, the NLS is fused to the N-terminus of the deaminase. In some embodiments, the NLS is fused to the C-terminus of the deaminase. In some embodiments, the NLS is fused to the N-terminus of the second Cas9. In some embodiments, the NLS is fused to the C-terminus of the second Cas9. In some embodiments, the NLS is fused to the fusion protein via one or more linkers. In some embodiments, the NLS is fused to the fusion protein without a linker. In some embodiments, the NLS comprises an amino acid sequence of any one of the NLS sequences provided or referenced herein. In some embodiments, the NLS comprises an amino acid sequence as set forth in SEQ ID NO: 741 or SEQ ID NO: 742.


In some embodiments, a UGI domain comprises a wild-type UGI or a UGI as set forth in SEQ ID NO: 600. In some embodiments, the UGI proteins provided herein include fragments of UGI and proteins homologous to a UGI or a UGI fragment. For example, in some embodiments, a UGI domain comprises a fragment of the amino acid sequence set forth in SEQ ID NO: 600. In some embodiments, a UGI fragment comprises an amino acid sequence that comprises at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or at least 99.5% of the amino acid sequence as set forth in SEQ ID NO: 600. In some embodiments, a UGI comprises an amino acid sequence homologous to the amino acid sequence set forth in SEQ ID NO: 600 or an amino acid sequence homologous to a fragment of the amino acid sequence set forth in SEQ ID NO: 600. In some embodiments, proteins comprising UGI or fragments of UGI or homologs of UGI or UGI fragments are referred to as “UGI variants.” A UGI variant shares homology to UGI, or a fragment thereof. For example a UGI variant is at least 70% identical, at least 75% identical, at least 80% identical, at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical, at least 99.5% identical, or at least 99.9% identical to a wild type UGI or a UGI as set forth in SEQ ID NO: 600. In some embodiments, the UGI variant comprises a fragment of UGI, such that the fragment is at least 70% identical, at least 80% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 97% identical, at least 98% identical, at least 99% identical, at least 99.5% identical, or at least 99.9% to the corresponding fragment of wild-type UGI or a UGI as set forth in SEQ ID NO: 600. In some embodiments, the UGI comprises the following amino acid sequence:

    • >sp|P14739|UNGI_BPPB2 Uracil-DNA glycosylase inhibitor MTNLSDIIEKETGKQLVIQESILMLPEEVEEVIGNKPESDILVHTAYDESTDENVMLLTSDA PEYKPWALVIQDSNGENKIKML (SEQ ID NO: 600)


Suitable UGI protein and nucleotide sequences are provided herein and additional suitable UGI sequences are known to those in the art, and include, for example, those published in Wang et al., Uracil-DNA glycosylase inhibitor gene of bacteriophage PBS2 encodes a binding protein specific for uracil-DNA glycosylase. J. Biol. Chem. 264:1163-1171(1989); Lundquist et al., Site-directed mutagenesis and characterization of uracil-DNA glycosylase inhibitor protein. Role of specific carboxylic amino acids in complex formation with Escherichia coli uracil-DNA glycosylase. J. Biol. Chem. 272:21408-21419(1997); Ravishankar et al., X-ray analysis of a complex of Escherichia coli uracil DNA glycosylase (EcUDG) with a proteinaceous inhibitor. The structure elucidation of a prokaryotic UDG. Nucleic Acids Res. 26:4880-4887(1998); and Putnam et al., Protein mimicry of DNA from crystal structures of the uracil-DNA glycosylase inhibitor protein and its complex with Escherichia coli uracil-DNA glycosylase. J. Mol. Biol. 287:331-346(1999), the entire contents of each are incorporated herein by reference.


It should be appreciated that additional proteins may be uracil glycosylase inhibitors. For example, other proteins that are capable of inhibiting (e.g., sterically blocking) a uracil-DNA glycosylase base-excision repair enzyme are within the scope of this disclosure. Additionally, any proteins that block or inhibit base-excision repair as also within the scope of this disclosure. In some embodiments, a protein that binds DNA is used. In another embodiment, a substitute for UGI is used. In some embodiments, a uracil glycosylase inhibitor is a protein that binds single-stranded DNA. For example, a uracil glycosylase inhibitor may be a Erwinia tasmaniensis single-stranded binding protein. In some embodiments, the single-stranded binding protein comprises the amino acid sequence (SEQ ID NO: 322). In some embodiments, a uracil glycosylase inhibitor is a protein that binds uracil. In some embodiments, a uracil glycosylase inhibitor is a protein that binds uracil in DNA. In some embodiments, a uracil glycosylase inhibitor is a catalytically inactive uracil DNA-glycosylase protein. In some embodiments, a uracil glycosylase inhibitor is a catalytically inactive uracil DNA-glycosylase protein that does not excise uracil from the DNA. For example, a uracil glycosylase inhibitor is a UdgX. In some embodiments, the UdgX comprises the amino acid sequence (SEQ ID NO: 323). As another example, a uracil glycosylase inhibitor is a catalytically inactive UDG. In some embodiments, a catalytically inactive UDG comprises the amino acid sequence (SEQ ID NO: 324). It should be appreciated that other uracil glycosylase inhibitors would be apparent to the skilled artisan and are within the scope of this disclosure. In some embodiments, a uracil glycosylase inhibitor is a protein that is homologous to any one of SEQ ID NOs: 322-324. In some embodiments, a uracil glycosylase inhibitor is a protein that is at least 50% identical, at least 55% identical at least 60% identical, at least 65% identical, at least 70% identical, at least 75% identical, at least 80% identical at least 85% identical, at least 90% identical, at least 95% identical, at least 96% identical, at least 98% identical, at least 99% identical, or at least 99.5% identical to any one of SEQ ID NOs: 322-324.










Erwinia tasmaniensis SSB



(themostable single-stranded DNA binding protein)


(SEQ ID NO: 322)


MASRGVNKVILVGNLGQDPEVRYMPNGGAVANITLATSESWRDKQTGETK





EKTEWHRVVLFGKLAEVAGEYLRKGSQVYIEGALQTRKWTDQAGVEKYTT





EVVVNVGGTMQMLGGRSQGGGASAGGQNGGSNNGWGQPQQPQGGNQFSGG





AQQQARPQQQPQQNNAPANNEPPIDFDDDIP





UdgX (binds to Uracil in DNA but does not excise)


(SEQ ID NO: 323)


MAGAQDFVPHTADLAELAAAAGECRGCGLYRDATQAVFGAGGRSARIMMI





GEQPGDKEDLAGLPFVGPAGRLLDRALEAADIDRDALYVTNAVKHFKFTR





AAGGKRRIHKTPSRTEVVACRPWLIAEMTSVEPDVVVLLGATAAKALLGN





DFRVTQHRGEVLHVDDVPGDPALVATVHPSSLLRGPKEERESAFAGLVDD





LRVAADVRP





UDG (catalytically inactive human UDG, binds to


Uracil in DNA but does not excise)


(SEQ ID NO: 324)


MIGQKTLYSFFSPSPARKRHAPSPEPAVQGTGVAGVPEESGDAAAIPAKK





APAGQEEPGTPPSSPLSAEQLDRIQRNKAAALLRLAARNVPVGFGESWKK





HLSGEFGKPYFIKLMGFVAEERKHYTVYPPPHQVFTWTQMCDIKDVKVVI





LGQEPYHGPNQAHGLCFSVQRPVPPPPSLENIYKELSTDIEDFVHPGHGD





LSGWAKQGVLLLNAVLTVRAHQANSHKERGWEQFTDAVVSWLNQNSNGLV





FLLWGSYAQKKGSAIDRKRHHVLQTAHPSPLSVYRGFFGCRHFSKTNELL





QKSGKKPIDWKEL






In some embodiments, the nucleic acid editing domain is a deaminase domain. In some embodiments, the deaminase is a cytosine deaminase or a cytidine deaminase. In some embodiments, the deaminase is an apolipoprotein B mRNA-editing complex (APOBEC) family deaminase. In some embodiments, the deaminase is an APOBEC1 deaminase. In some embodiments, the deaminase is an APOBEC2 deaminase. In some embodiments, the deaminase is an APOBEC3 deaminase. In some embodiments, the deaminase is an APOBEC3A deaminase. In some embodiments, the deaminase is an APOBEC3B deaminase. In some embodiments, the deaminase is an APOBEC3C deaminase. In some embodiments, the deaminase is an APOBEC3D deaminase. In some embodiments, the deaminase is an APOBEC3E deaminase. In some embodiments, the deaminase is an APOBEC3F deaminase. In some embodiments, the deaminase is an APOBEC3G deaminase. In some embodiments, the deaminase is an APOBEC3H deaminase. In some embodiments, the deaminase is an APOBEC4 deaminase. In some embodiments, the deaminase is an activation-induced deaminase (AID). In some embodiments, the deaminase is a rat APOBEC1 (SEQ ID NO: 282). In some embodiments, the deminase is a human APOBEC1 (SEQ ID No: 284). In some embodiments, the deaminase is a Petromyzon marinus cytidine deaminase 1 (pmCDA1). In some embodiments, the deminase is a human APOBEC3G (SEQ ID NO: 275). In some embodiments, the deaminase is a fragment of the human APOBEC3G (SEQ ID NO: 5740). In some embodiments, the deaminase is a human APOBEC3G variant comprising a D316R_D317R mutation (SEQ ID NO: 5739). In some embodiments, the deaminase is a frantment of the human APOBEC3G and comprising mutations corresponding to the D316R_D317R mutations in SEQ ID NO: 275 (SEQ ID NO: 5741).


In some embodiments, the linker comprises a (GGGS)n (SEQ ID NO: 265), (GGGGS)n (SEQ ID NO: 5), a (G)n, an (EAAAK)n (SEQ ID NO: 6), a (GGS)n, an SGSETPGTSESATPES (SEQ ID NO: 7), or an (XP)n motif, or a combination of any of these, wherein n is independently an integer between 1 and 30.


Suitable UGI protein and nucleotide sequences are provided herein and additional suitable UGI sequences are known to those in the art, and include, for example, those published in Wang et al., Uracil-DNA glycosylase inhibitor gene of bacteriophage PBS2 encodes a binding protein specific for uracil-DNA glycosylase. J. Biol. Chem. 264:1163-1171(1989); Lundquist et al., Site-directed mutagenesis and characterization of uracil-DNA glycosylase inhibitor protein. Role of specific carboxylic amino acids in complex formation with Escherichia coli uracil-DNA glycosylase. J. Biol. Chem. 272:21408-21419(1997); Ravishankar et al., X-ray analysis of a complex of Escherichia coli uracil DNA glycosylase (EcUDG) with a proteinaceous inhibitor. The structure elucidation of a prokaryotic UDG. Nucleic Acids Res. 26:4880-4887(1998); and Putnam et al., Protein mimicry of DNA from crystal structures of the uracil-DNA glycosylase inhibitor protein and its complex with Escherichia coli uracil-DNA glycosylase. J. Mol. Biol. 287:331-346(1999), the entire contents of which are incorporated herein by reference. In some embodiments, the optional linker comprises a (GGS)n motif, wherein n is 1, 2, 3, 4, 5, 6, 7, 8, 9, 19, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20. In some embodiments, the optional linker comprises a (GGS)n motif, wherein n is 1, 3, or 7. In some embodiments, the optional linker comprises the amino acid sequence SGSETPGTSESATPES (SEQ ID NO: 7), which is also referred to as the XTEN linker in the Examples.


In some embodiments, a Cas9 nickase may further facilitate the removal of a base on the non-edited strand in an organism whose genome is edited in vivo. The Cas9 nickase, as described herein, may comprise a D10A mutation in SEQ ID NO: 10, or a corresponding mutation in any of SEQ ID NOs: 11-260. In some embodiments, the Cas9 nickase of this disclosure may comprise a histidine at mutation 840 of SEQ ID NO: 10, or a corresponding residue in any of SEQ ID NOs: 11-260. Such fusion proteins comprising the Cas9 nickase, can cleave a single strand of the target DNA sequence, e.g., the strand that is not being edited. Without wishing to be bound by any particular theory, this cleavage may inhibit mis-match repair mechanisms that reverse a C to U edit made by the deaminase.


Cas9 Complexes with Guide RNAs


Some aspects of this disclosure provide complexes comprising any of the fusion proteins provided herein, and a guide RNA bound to a Cas9 domain (e.g., a dCas9, a nuclease active Cas9, or a Cas9 nickase) of fusion protein.


In some embodiments, the guide RNA is from 15-100 nucleotides long and comprises a sequence of at least 10 contiguous nucleotides that is complementary to a target sequence. In some embodiments, the guide RNA is 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 nucleotides long. In some embodiments, the guide RNA comprises a sequence of 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 contiguous nucleotides that is complementary to a target sequence. In some embodiments, the target sequence is a DNA sequence. In some embodiments, the target sequence is a sequence in the genome of a mammal. In some embodiments, the target sequence is a sequence in the genome of a human. In some embodiments, the 3′ end of the target sequence is immediately adjacent to a canonical PAM sequence (NGG). In some embodiments, the guide RNA is complementary to a sequence associated with a disease or disorder. In some embodiments, the guide RNA is complementary to a sequence associated with a disease or disorder having a mutation in a gene selected from the genes disclosed in any one of Tables 1-3. In some embodiments, the guide RNA comprises a nucleotide sequence of any one of the guide sequences provided in Table 2 or Table 3. Exemplary sequences in the human genome that may be targeted by the complexes of this disclosure are provided herein in Tables 1-3.


Methods of Using Cas9 Fusion Proteins


Some aspects of this disclosure provide methods of using the Cas9 proteins, fusion proteins, or complexes provided herein. For example, some aspects of this disclosure provide methods comprising contacting a DNA molecule (a) with any of the the Cas9 proteins or fusion proteins provided herein, and with at least one guide RNA, wherein the guide RNA is about 15-100 nucleotides long and comprises a sequence of at least 10 contiguous nucleotides that is complementary to a target sequence; or (b) with a Cas9 protein, a Cas9 fusion protein, or a Cas9 protein or fusion protein complex with at least one gRNA as provided herein. In some embodiments, the 3′ end of the target sequence is not immediately adjacent to a canonical PAM sequence (NGG). In some embodiments, the 3′ end of the target sequence is immediately adjacent to an AGC, GAG, TTT, GTG, or CAA sequence.


In some embodiments, the target DNA sequence comprises a sequence associated with a disease or disorder. In some embodiments, the target DNA sequence comprises a point mutation associated with a disease or disorder. In some embodiments, the activity of the Cas9 protein, the Cas9 fusion protein, or the complex results in a correction of the point mutation. In some embodiments, the target DNA sequence comprises a T→C point mutation associated with a disease or disorder, and wherein the deamination of the mutant C base results in a sequence that is not associated with a disease or disorder. In some embodiments, the target DNA sequence encodes a protein and wherein the point mutation is in a codon and results in a change in the amino acid encoded by the mutant codon as compared to the wild-type codon. In some embodiments, the deamination of the mutant C results in a change of the amino acid encoded by the mutant codon. In some embodiments, the deamination of the mutant C results in the codon encoding the wild-type amino acid. In some embodiments, the contacting is in vivo in a subject. In some embodiments, the subject has or has been diagnosed with a disease or disorder. In some embodiments, the disease or disorder is cystic fibrosis, phenylketonuria, epidermolytic hyperkeratosis (EHK), Charcot-Marie-Toot disease type 4J, neuroblastoma (NB), von Willebrand disease (vWD), myotonia congenital, hereditary renal amyloidosis, dilated cardiomyopathy (DCM), hereditary lymphedema, familial Alzheimer's disease, HIV, Prion disease, chronic infantile neurologic cutaneous articular syndrome (CINCA), desmin-related myopathy (DRM), a neoplastic disease associated with a mutant PI3KCA protein, a mutant CTNNB1 protein, a mutant HRAS protein, or a mutant p53 protein.


Some embodiments provide methods for using the Cas9 DNA editing fusion proteins provided herein. In some embodiments, the fusion protein is used to introduce a point mutation into a nucleic acid by deaminating a target nucleobase, e.g., a C residue. In some embodiments, the deamination of the target nucleobase results in the correction of a genetic defect, e.g., in the correction of a point mutation that leads to a loss of function in a gene product. In some embodiments, the genetic defect is associated with a disease or disorder, e.g., a lysosomal storage disorder or a metabolic disease, such as, for example, type I diabetes. In some embodiments, the methods provided herein are used to introduce a deactivating point mutation into a gene or allele that encodes a gene product that is associated with a disease or disorder. For example, in some embodiments, methods are provided herein that employ a Cas9 DNA editing fusion protein to introduce a deactivating point mutation into an oncogene (e.g., in the treatment of a proliferative disease). A deactivating mutation may, in some embodiments, generate a premature stop codon in a coding sequence, which results in the expression of a truncated gene product, e.g., a truncated protein lacking the function of the full-length protein.


In some embodiments, the purpose of the methods provide herein is to restore the function of a dysfunctional gene via genome editing. The Cas9 deaminase fusion proteins provided herein can be validated for gene editing-based human therapeutics in vitro, e.g., by correcting a disease-associated mutation in human cell culture. It will be understood by the skilled artisan that the fusion proteins provided herein, e.g., the fusion proteins comprising a Cas9 domain and a nucleic acid deaminase domain can be used to correct any single point T->C or A->G mutation. In the first case, deamination of the mutant C back to U corrects the mutation, and in the latter case, deamination of the C that is base-paired with the mutant G, followed by a round of replication, corrects the mutation.


An exemplary disease-relevant mutation that can be corrected by the provided fusion proteins in vitro or in vivo is the H1047R (A3140G) polymorphism in the PI3KCA protein. The phosphoinositide-3-kinase, catalytic alpha subunit (PI3KCA) protein acts to phosphorylate the 3-OH group of the inositol ring of phosphatidylinositol. The PI3KCA gene has been found to be mutated in many different carcinomas, and thus it is considered to be a potent oncogene.37 In fact, the A3140G mutation is present in several NCI-60 cancer cell lines, such as, for example, the HCT116, SKOV3, and T47D cell lines, which are readily available from the American Type Culture Collection (ATCC).38


In some embodiments, a cell carrying a mutation to be corrected, e.g., a cell carrying a point mutation, e.g., an A3140G point mutation in exon 20 of the PI3KCA gene, resulting in a H1047R substitution in the PI3KCA protein, is contacted with an expression construct encoding a Cas9 deaminase fusion protein and an appropriately designed sgRNA targeting the fusion protein to the respective mutation site in the encoding PI3KCA gene. Control experiments can be performed where the sgRNAs are designed to target the fusion enzymes to non-C residues that are within the PI3KCA gene. Genomic DNA of the treated cells can be extracted, and the relevant sequence of the PI3KCA genes PCR amplified and sequenced to assess the activities of the fusion proteins in human cell culture.


It will be understood that the example of correcting point mutations in PI3KCA is provided for illustration purposes and is not meant to limit the instant disclosure. The skilled artisan will understand that the instantly disclosed DNA-editing fusion proteins can be used to correct other point mutations and mutations associated with other cancers and with diseases other than cancer including other proliferative diseases.


The successful correction of point mutations in disease-associated genes and alleles opens up new strategies for gene correction with applications in therapeutics and basic research. Site-specific single-base modification systems like the disclosed fusions of Cas9 and deaminase enzymes or domains also have applications in “reverse” gene therapy, where certain gene functions are purposely suppressed or abolished. In these cases, site-specifically mutating Trp (TGG), Gln (CAA and CAG), or Arg (CGA) residues to premature stop codons (TAA, TAG, TGA) can be used to abolish protein function in vitro, ex vivo, or in vivo.


The instant disclosure provides methods for the treatment of a subject diagnosed with a disease associated with or caused by a point mutation that can be corrected by a Cas9 DNA editing fusion protein provided herein. For example, in some embodiments, a method is provided that comprises administering to a subject having such a disease, e.g., a cancer associated with a PI3KCA point mutation as described above, an effective amount of a Cas9 deaminase fusion protein that corrects the point mutation or introduces a deactivating mutation into the disease-associated gene. In some embodiments, the disease is a proliferative disease. In some embodiments, the disease is a genetic disease. In some embodiments, the disease is a neoplastic disease. In some embodiments, the disease is a metabolic disease. In some embodiments, the disease is a lysosomal storage disease. Other diseases that can be treated by correcting a point mutation or introducing a deactivating mutation into a disease-associated gene will be known to those of skill in the art, and the disclosure is not limited in this respect.


The instant disclosure provides methods for the treatment of additional diseases or disorders, e.g., diseases or disorders that are associated or caused by a point mutation that can be corrected by deaminase-mediated gene editing. Some such diseases are described herein, and additional suitable diseases that can be treated with the strategies and fusion proteins provided herein will be apparent to those of skill in the art based on the instant disclosure. Exemplary suitable diseases and disorders are listed below. It will be understood that the numbering of the specific positions or residues in the respective sequences depends on the particular protein and numbering scheme used. Numbering might be different, e.g., in precursors of a mature protein and the mature protein itself, and differences in sequences from species to species may affect numbering. One of skill in the art will be able to identify the respective residue in any homologous protein and in the respective encoding nucleic acid by methods well known in the art, e.g., by sequence alignment and determination of homologous residues. Exemplary suitable diseases and disorders include, without limitation, cystic fibrosis (see, e.g., Schwank et al., Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell stem cell. 2013; 13: 653-658; and Wu et. al., Correction of a genetic disease in mouse via use of CRISPR-Cas9. Cell stem cell. 2013; 13: 659-662, neither of which uses a deaminase fusion protein to correct the genetic defect); phenylketonuria—e.g., phenylalanine to serine mutation at position 835 (mouse) or 240 (human) or a homologous residue in phenylalanine hydroxylase gene (T>C mutation)—see, e.g., McDonald et al., Genomics. 1997; 39:402-405; Bernard-Soulier syndrome (BSS)—e.g., phenylalanine to serine mutation at position 55 or a homologous residue, or cysteine to arginine at residue 24 or a homologous residue in the platelet membrane glycoprotein IX (T>C mutation)—see, e.g., Noris et al., British Journal of Haematology. 1997; 97: 312-320, and Ali et al., Hematol. 2014; 93: 381-384; epidermolytic hyperkeratosis (EHK)—e.g., leucine to proline mutation at position 160 or 161 (if counting the initiator methionine) or a homologous residue in keratin 1 (T>C mutation)—see, e.g., Chipev et al., Cell. 1992; 70: 821-828, see also accession number P04264 in the UNIPROT database at www[dot]uniprot[dot]org; chronic obstructive pulmonary disease (COPD)—e.g., leucine to proline mutation at position 54 or 55 (if counting the initiator methionine) or a homologous residue in the processed form of α1-antitrypsin or residue 78 in the unprocessed form or a homologous residue (T>C mutation)—see, e.g., Poller et al., Genomics. 1993; 17: 740-743, see also accession number P01011 in the UNIPROT database; Charcot-Marie-Toot disease type 4J—e.g., isoleucine to threonine mutation at position 41 or a homologous residue in FIG. 4 (T>C mutation)—see, e.g., Lenk et al., PLoS Genetics. 2011; 7: e1002104; neuroblastoma (NB)—e.g., leucine to proline mutation at position 197 or a homologous residue in Caspase-9 (T>C mutation)—see, e.g., Kundu et al., 3 Biotech. 2013, 3:225-234; von Willebrand disease (vWD)—e.g., cysteine to arginine mutation at position 509 or a homologous residue in the processed form of von Willebrand factor, or at position 1272 or a homologous residue in the unprocessed form of von Willebrand factor (T>C mutation)—see, e.g., Lavergne et al., Br. J. Haematol. 1992, see also accession number P04275 in the UNIPROT database; 82: 66-72; myotonia congenital—e.g., cysteine to arginine mutation at position 277 or a homologous residue in the muscle chloride channel gene CLCN1 (T>C mutation)—see, e.g., Weinberger et al., The J. of Physiology. 2012; 590: 3449-3464; hereditary renal amyloidosis—e.g., stop codon to arginine mutation at position 78 or a homologous residue in the processed form of apolipoprotein AII or at position 101 or a homologous residue in the unprocessed form (T>C mutation)—see, e.g., Yazaki et al., Kidney Int. 2003; 64: 11-16; dilated cardiomyopathy (DCM)—e.g., tryptophan to Arginine mutation at position 148 or a homologous residue in the FOXD4 gene (T>C mutation), see, e.g., Minoretti et. al., Int. J. of Mol. Med. 2007; 19: 369-372; hereditary lymphedema—e.g., histidine to arginine mutation at position 1035 or a homologous residue in VEGFR3 tyrosine kinase (A>G mutation), see, e.g., Irrthum et al., Am. J. Hum. Genet. 2000; 67: 295-301; familial Alzheimer's disease—e.g., isoleucine to valine mutation at position 143 or a homologous residue in presenilin1 (A>G mutation), see, e.g., Gallo et. al., J. Alzheimer's disease. 2011; 25: 425-431; Prion disease—e.g., methionine to valine mutation at position 129 or a homologous residue in prion protein (A>G mutation)—see, e.g., Lewis et. al., J. of General Virology. 2006; 87: 2443-2449; chronic infantile neurologic cutaneous articular syndrome (CINCA)—e.g., Tyrosine to Cysteine mutation at position 570 or a homologous residue in cryopyrin (A>G mutation)—see, e.g., Fujisawa et. al. Blood. 2007; 109: 2903-2911; and desmin-related myopathy (DRM)—e.g., arginine to glycine mutation at position 120 or a homologous residue in αβ crystallin (A>G mutation)—see, e.g., Kumar et al., J. Biol. Chem. 1999; 274: 24137-24141. The entire contents of all references and database entries is incorporated herein by reference.


The instant disclosure provides lists of genes comprising pathogenic T>C or A>G mutations. Provided herein, are the names of these genes, their respective SEQ ID NOs, their gene IDs, and sequences flanking the mutation site. (Tables 2 and 3). In some instances, the gRNA sequences that can be used to correct the mutations in these genes are disclosed (Tables 2 and 3).


In some embodiments, a Cas9-deaminase fusion protein recognizes canonical PAMs and therefore can correct the pathogenic T>C or A>G mutations with canonical PAMs, e.g., NGG (listed in Tables 2 and 3, SEQ ID NOs: 2540-2702 and 5084-5260), respectively, in the flanking sequences. For example, the Cas9 proteins that recognize canonical PAMs comprise an amino acid sequence that is at least 90% identical to the amino acid sequence of Streptococcus pyogenes Cas9 as provided by SEQ ID NO: 10, or to a fragment thereof comprising the RuvC and HNH domains of SEQ ID NO: 10.


It will be apparent to those of skill in the art that in order to target a Cas9:nucleic acid editing enzyme/domain fusion protein as disclosed herein to a target site, e.g., a site comprising a point mutation to be edited, it is typically necessary to co-express the Cas9:nucleic acid editing enzyme/domain fusion protein together with a guide RNA, e.g., an sgRNA. As explained in more detail elsewhere herein, a guide RNA typically comprises a tracrRNA framework allowing for Cas9 binding, and a guide sequence, which confers sequence specificity to the Cas9:nucleic acid editing enzyme/domain fusion protein. In some embodiments, the guide RNA comprises a structure 5′-[guide sequence]-guuuuagagcuagaaauagcaaguuaaaauaaaggcuaguccguuaucaacuugaaaaaguggcaccgagucggugcuuuuu-3′ (SEQ ID NO: 601), wherein the guide sequence comprises a sequence that is complementary to the target sequence. The guide sequence is typically 20 nucleotides long. The sequences of suitable guide RNAs for targeting Cas9:nucleic acid editing enzyme/domain fusion proteins to specific genomic target sites will be apparent to those of skill in the art based on the instant disclosure. Such suitable guide RNA sequences typically comprise guide sequences that are complementary to a nucleic sequence within 50 nucleotides upstream or downstream of the target nucleotide to be edited. Some exemplary guide RNA sequences suitable for targeting Cas9:nucleic acid editing enzyme/domain fusion proteins to specific target sequences are provided below.


Base Editor Efficiency


Some aspects of the disclosure are based on the recognition that any of the base editors provided herein are capable of modifying a specific nucleotide base without generating a significant proportion of indels. An “indel”, as used herein, refers to the insertion or deletion of a nucleotide base within a nucleic acid. Such insertions or deletions can lead to frame shift mutations within a coding region of a gene. In some embodiments, it is desirable to generate base editors that efficiently modify (e.g. mutate or deaminate) a specific nucleotide within a nucleic acid, without generating a large number of insertions or deletions (i.e., indels) in the nucleic acid. In certain embodiments, any of the base editors provided herein are capable of generating a greater proportion of intended modifications (e.g., point mutations or deaminations) versus indels. In some embodiments, the base editors provided herein are capable of generating a ratio of intended point mutations to indels that is greater than 1:1. In some embodiments, the base editors provided herein are capable of generating a ratio of intended point mutations to indels that is at least 1.5:1, at least 2:1, at least 2.5:1, at least 3:1, at least 3.5:1, at least 4:1, at least 4.5:1, at least 5:1, at least 5.5:1, at least 6:1, at least 6.5:1, at least 7:1, at least 7.5:1, at least 8:1, at least 10:1, at least 12:1, at least 15:1, at least 20:1, at least 25:1, at least 30:1, at least 40:1, at least 50:1, at least 100:1, at least 200:1, at least 300:1, at least 400:1, at least 500:1, at least 600:1, at least 700:1, at least 800:1, at least 900:1, or at least 1000:1, or more. The number of intended mutations and indels may be determined using any suitable method, for example the methods used in the below Examples.


In some embodiments, the base editors provided herein are capable of limiting formation of indels in a region of a nucleic acid. In some embodiments, the region is at a nucleotide targeted by a base editor or a region within 2, 3, 4, 5, 6, 7, 8, 9, or 10 nucleotides of a nucleotide targeted by a base editor. In some embodiments, any of the base editors provided herein are capable of limiting the formation of indels at a region of a nucleic acid to less than 1%, less than 1.5%, less than 2%, less than 2.5%, less than 3%, less than 3.5%, less than 4%, less than 4.5%, less than 5%, less than 6%, less than 7%, less than 8%, less than 9%, less than 10%, less than 12%, less than 15%, or less than 20%. The number of indels formed at a nucleic acid region may depend on the amount of time a nucleic acid (e.g., a nucleic acid within the genome of a cell) is exposed to a base editor. In some embodiments, an number or proportion of indels is determined after at least 1 hour, at least 2 hours, at least 6 hours, at least 12 hours, at least 24 hours, at least 36 hours, at least 48 hours, at least 3 days, at least 4 days, at least 5 days, at least 7 days, at least 10 days, or at least 14 days of exposing a nucleic acid (e.g., a nucleic acid within the genome of a cell) to a base editor.


Some aspects of the disclosure are based on the recognition that any of the base editors provided herein are capable of efficiently generating an intended mutation, such as a point mutation, in a nucleic acid (e.g. a nucleic acid within a genome of a subject) without generating a significant number of unintended mutations, such as unintended point mutations. In some embodiments, a intended mutation is a mutation that is generated by a specific base editor bound to a gRNA, specifically designed to generate the intended mutation. In some embodiments, the intended mutation is a mutation associated with a disease or disorder. In some embodiments, the intended mutation is a cytosine (C) to thymine (T) point mutation associated with a disease or disorder. In some embodiments, the intended mutation is a guanine (G) to adenine (A) point mutation associated with a disease or disorder. In some embodiments, the intended mutation is a cytosine (C) to thymine (T) point mutation within the coding region of a gene. In some embodiments, the intended mutation is a guanine (G) to adenine (A) point mutation within the coding region of a gene. In some embodiments, the intended mutation is a point mutation that generates a stop codon, for example, a premature stop codon within the coding region of a gene. In some embodiments, the intended mutation is a mutation that eliminates a stop codon. In some embodiments, the intended mutation is a mutation that alters the splicing of a gene. In some embodiments, the intended mutation is a mutation that alters the regulatory sequence of a gene (e.g., a gene promotor or gene repressor). In some embodiments, any of the base editors provided herein are capable of generating a ratio of intended mutations to unintended mutations (e.g., intended point mutations:unintended point mutations) that is greater than 1:1. In some embodiments, any of the base editors provided herein are capable of generating a ratio of intended mutations to unintended mutations (e.g., intended point mutations:unintended point mutations) that is at least 1.5:1, at least 2:1, at least 2.5:1, at least 3:1, at least 3.5:1, at least 4:1, at least 4.5:1, at least 5:1, at least 5.5:1, at least 6:1, at least 6.5:1, at least 7:1, at least 7.5:1, at least 8:1, at least 10:1, at least 12:1, at least 15:1, at least 20:1, at least 25:1, at least 30:1, at least 40:1, at least 50:1, at least 100:1, at least 150:1, at least 200:1, at least 250:1, at least 500:1, or at least 1000:1, or more. It should be appreciated that the characteristics of the base editors described in the “Base Editor Efficiency” section, herein, may be applied to any of the fusion proteins, or methods of using the fusion proteins provided herein.


Methods for Editing Nucleic Acids


Some aspects of the disclosure provide methods for editing a nucleic acid. In some embodiments, the method is a method for editing a nucleobase of a nucleic acid (e.g., a base pair of a double-stranded DNA sequence). In some embodiments, the method comprises the steps of: a) contacting a target region of a nucleic acid (e.g., a double-stranded DNA sequence) with a complex comprising a base editor (e.g., a Cas9 domain fused to a cytidine deaminase domain) and a guide nucleic acid (e.g., gRNA), wherein the target region comprises a targeted nucleobase pair, b) inducing strand separation of said target region, c)converting a first nucleobase of said target nucleobase pair in a single strand of the target region to a second nucleobase, and d) cutting no more than one strand of said target region, where a third nucleobase complementary to the first nucleobase base is replaced by a fourth nucleobase complementary to the second nucleobase; and the method results in less than 20% indel formation in the nucleic acid. It should be appreciated that in some embodiments, step b is omitted. In some embodiments, the first nucleobase is a cytosine. In some embodiments, the second nucleobase is a deaminated cytosine, or a uracil. In some embodiments, the third nucleobase is a guanine. In some embodiments, the fourth nucleobase is an adenine. In some embodiments, the first nucleobase is a cytosine, the second nucleobase is a deaminated cytosine, or a uracil, the third nucleobase is a guanine, and the fourth nucleobase is an adenine. In some embodiments, the method results in less than 19%, 18%, 16%, 14%, 12%, 10%, 8%, 6%, 4%, 2%, 1%, 0.5%, 0.2%, or less than 0.1% indel formation. In some embodiments, the method further comprises replacing the second nucleobase with a fifth nucleobase that is complementary to the fourth nucleobase, thereby generating an intended edited base pair (e.g., C:G→T:A). In some embodiments, the fifth nucleobase is a thymine. In some embodiments, at least 5% of the intended basepairs are edited. In some embodiments, at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% of the intended basepairs are edited.


In some embodiments, the ratio of intended products to unintended products in the target nucleotide is at least 2:1, 5:1, 10:1, 20:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90:1, 100:1, or 200:1, or more. In some embodiments, the ratio of intended point mutation to indel formation is greater than 1:1, 10:1, 50:1, 100:1, 500:1, or 1000:1, or more. In some embodiments, the cut single strand (nicked strand) is hybridized to the guide nucleic acid. In some embodiments, the cut single strand is opposite to the strand comprising the first nucleobase. In some embodiments, the base editor comprises a Cas9 domain. In some embodiments, the first base is cytosine, and the second base is not a G, C, A, or T. In some embodiments, the second base is uracil. In some embodiments, the first base is cytosine. In some embodiments, the second base is not a G, C, A, or T. In some embodiments, the second base is uracil. In some embodiments, the base editor inhibits base excision repair of the edited strand. In some embodiments, the base editor protects or binds the non-edited strand. In some embodiments, the base editor comprises UGI activity. In some embodiments, the base editor comprises nickase activity. In some embodiments, the intended edited basepair is upstream of a PAM site. In some embodiments, the intended edited base pair is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleotides upstream of the PAM site. In some embodiments, the intended edited basepair is downstream of a PAM site. In some embodiments, the intended edited base pair is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleotides downstream stream of the PAM site. In some embodiments, the method does not require a canonical (e.g., NGG) PAM site. In some embodiments, the nucleobase editor comprises a linker. In some embodiments, the linker is 1-25 amino acids in length. In some embodiments, the linker is 5-20 amino acids in length. In some embodiments, linker is 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids in length. In some embodiments, the target region comprises a target window, wherein the target window comprises the target nucleobase pair. In some embodiments, the target window comprises 1-10 nucleotides. In some embodiments, the target window is 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, or 1 nucleotides in length. In some embodiments, the target window is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleotides in length. In some embodiments, the intended edited base pair is within the target window. In some embodiments, the target window comprises the intended edited base pair. In some embodiments, the method is performed using any of the base editors provided herein. In some embodiments, a target window is a deamination window


In some embodiments, the disclosure provides methods for editing a nucleotide. In some embodiments, the disclosure provides a method for editing a nucleobase pair of a double-stranded DNA sequence. In some embodiments, the method comprises a) contacting a target region of the double-stranded DNA sequence with a complex comprising a base editor and a guide nucleic acid (e.g., gRNA), where the target region comprises a target nucleobase pair, b) inducing strand separation of said target region, c) converting a first nucleobase of said target nucleobase pair in a single strand of the target region to a second nucleobase, d) cutting no more than one strand of said target region, wherein a third nucleobase complementary to the first nucleobase base is replaced by a fourth nucleobase complementary to the second nucleobase, and the second nucleobase is replaced with a fifth nucleobase that is complementary to the fourth nucleobase, thereby generating an intended edited basepair, wherein the efficiency of generating the intended edited basepair is at least 5%. It should be appreciated that in some embodiments, step b is omitted. In some embodiments, at least 5% of the intended basepairs are edited. In some embodiments, at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% of the intended basepairs are edited. In some embodiments, the method causes less than 19%, 18%, 16%, 14%, 12%, 10%, 8%, 6%, 4%, 2%, 1%, 0.5%, 0.2%, or less than 0.1% indel formation. In some embodiments, the ratio of intended product to unintended products at the target nucleotide is at least 2:1, 5:1, 10:1, 20:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90:1, 100:1, or 200:1, or more. In some embodiments, the ratio of intended point mutation to indel formation is greater than 1:1, 10:1, 50:1, 100:1, 500:1, or 1000:1, or more. In some embodiments, the cut single strand is hybridized to the guide nucleic acid. In some embodiments, the cut single strand is opposite to the strand comprising the first nucleobase. In some embodiments, the first base is cytosine. In some embodiments, the second nucleobase is not G, C, A, or T. In some embodiments, the second base is uracil. In some embodiments, the base editor inhibits base excision repair of the edited strand. In some embodiments, the base editor protects or binds the non-edited strand. In some embodiments, the nucleobase editor comprises UGI activity. In some embodiments, the nucleobase edit comprises nickase activity. In some embodiments, the intended edited basepair is upstream of a PAM site. In some embodiments, the intended edited base pair is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleotides upstream of the PAM site. In some embodiments, the intended edited basepair is downstream of a PAM site. In some embodiments, the intended edited base pair is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleotides downstream stream of the PAM site. In some embodiments, the method does not require a canonical (e.g., NGG) PAM site. In some embodiments, the nucleobase editor comprises a linker. In some embodiments, the linker is 1-25 amino acids in length. In some embodiments, the linker is 5-20 amino acids in length. In some embodiments, the linker is 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids in length. In some embodiments, the target region comprises a target window, wherein the target window comprises the target nucleobase pair. In some embodiments, the target window comprises 1-10 nucleotides. In some embodiments, the target window is 1-9, 1-8, 1-7, 1-6, 1-5, 1-4, 1-3, 1-2, or 1 nucleotides in length. 108/663 H0824.70213w000 In some embodiments, the target window is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 nucleotides in length. In some embodiments, the intended edited base pair occurs within the target window. In some embodiments, the target window comprises the intended edited base pair. In some embodiments, the nucleobase editor is any one of the base editors provided herein.


Kits, Vectors, Cells


Some aspects of this disclosure provide kits comprising a nucleic acid construct, comprising (a) a nucleotide sequence encoding a Cas9 protein or a Cas9 fusion protein as provided herein; and (b) a heterologous promoter that drives expression of the sequence of (a). In some embodiments, the kit further comprises an expression construct encoding a guide RNA backbone, wherein the construct comprises a cloning site positioned to allow the cloning of a nucleic acid sequence identical or complementary to a target sequence into the guide RNA backbone.


Some aspects of this disclosure provide polynucleotides encoding a Cas9 protein of a fusion protein as provided herein. Some aspects of this disclosure provide vectors comprising such polynucleotides. In some embodiments, the vector comprises a heterologous promoter driving expression of polynucleotide.


Some aspects of this disclosure provide cells comprising a Cas9 protein, a fusion protein, a nucleic acid molecule encoding the fusion protein, a complex comprise the Cas9 protein and the gRNA, and/or a vector as provided herein.


The description of exemplary embodiments of the reporter systems above is provided for illustration purposes only and not meant to be limiting. Additional reporter systems, e.g., variations of the exemplary systems described in detail above, are also embraced by this disclosure.


EXAMPLES
Example 1: Cas9 Deaminase Fusion Proteins

A number of Cas9:Deaminase fusion proteins were generated and deaminase activity of the generated fusions was characterized. The following deaminases were tested:









Human AID (hAID):


(SEQ ID NO: 607)


MDSLLMNRRKFLYQFKNVRWAKGRRETYLCYVVKRRDSATSFSLDFGYLR





NKNGCHVELLFLRYISDWDLDPGRCYRVTWFTSWSPCYDCARHVADFLRG





NPYLSLRIFTARLYFCEDRKAEPEGLRRLHRAGVQIAIMTFKDYFYCWNT





FVENHERTFKAWEGLHENSVRLSRQLRRILLPLYEVDDLRDAFRTLGLLD





Human AID-DC (hAID-DC, truncated version of hAID


with 7-fold increased activity):


(SEQ ID NO: 608)


MDSLLMNRRKFLYQFKNVRWAKGRRETYLCYVVKRRDSATSFSLDFGYLR





NKNGCHVELLFLRYISDWDLDPGRCYRVTWFTSWSPCYDCARHVADFLRG





NPNLSLRIFTARLYFCEDRKAEPEGLRRLHRAGVQIAIMTFKDYFYCWNT





FVENHERTFKAWEGLHENSVRLSRQLRRILL





Rat APOBEC1 (rAPOBEC1):


(SEQ ID NO: 284)


MSSETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSI





WRHTSQNTNKHVEVNFIEKFTTERYFCPNTRCSITWFLSWSPCGECSRAI





TEFLSRYPHVTLFIYIARLYHHADPRNRQGLRDLISSGVTIQIMTEQESG





YCWRNFVNYSPSNEAHWPRYPHLWVRLYVLELYCIILGLPPCLNILRRKQ





PQLTFFTIALQSCHYQRLPPHILWATGLK





Human APOBEC1 (hAPOBEC1)


(SEQ ID NO: 5724)


MTSEKGPSTGDPTLRRRIEPWEFDVFYDPRELRKEACLLYEIKWGMSRKI





WRSSGKNTTNHVEVNFIKKFTSERDFHPSMSCSITWFLSWSPCWECSQAI





REFLSRHPGVTLVIYVARLFWHMDQQNRQGLRDLVNSGVTIQIMRASEYY





HCWRNFVNYPPGDEAHWPQYPPLWMMLYALELHCIILSLPPCLKISRRWQ





NHLTFFRLHLQNCHYQTIPPHILLATGLIHPSVAWR





Petromyzon marinus (Lamprey) CDA1 (pmCDA1):


(SEQ ID NO: 609)


MTDAEYVRIHEKLDIYTFKKQFFNNKKSVSHRCYVLFELKRRGERRACFW





GYAVNKPQSGTERGIHAEIFSIRKVEEYLRDNPGQFTINWYSSWSPCADC





AEKILEWYNQELRGNGHTLKIWACKLYYEKNARNQIGLWNLRDNGVGLNV





MVSEHYQCCRKIFIQSSHNQLNENRWLEKTLKRAEKRRSELSIMIQVKIL





HTTKSPAV





Human APOBEC3G (hAPOBEC3G):


(SEQ ID NO: 610)


MELKYHPEMRFFHWFSKWRKLHRDQEYEVTWYISWSPCTKCTRDMATFLA





EDPKVTLTIFVARLYYFWDPDYQEALRSLCQKRDGPRATMKIMNYDEFQH





CWSKFVYSQRELFEPWNNLPKYYILLHIMLGEILRHSMDPPTFTFNFNNE





PWVRGRHETYLCYEVERMHNDTWVLLNQRRGFLCNQAPHKHGFLEGRHAE





LCFLDVIPFWKLDLDQDYRVTCFTSWSPCFSCAQEMAKFISKNKHVSLCI





FTARIYDDQGRCQEGLRTLAEAGAKISIMTYSEFKHCWDTFVDHQGCPFQ





PWDGLDEHSQDLSGRLRAILQNQEN






Deaminase Activity on ssDNA. A USER (Uracil-Specific Excision Reagent) Enzyme-based assay for deamination was employed to test the activity of various deaminases on single-stranded DNA (ssDNA) substrates. USER Enzyme was obtained from New England Biolabs. An ssDNA substrate was provided with a target cytosine residue at different positions. Deamination of the ssDNA cytosine target residue results in conversion of the target cytosine to a uracil. The USER Enzyme excises the uracil base and cleaves the ssDNA backbone at that position, cutting the ssDNA substrate into two shorter fragments of DNA. In some assays, the ssDNA substrate is labeled on one end with a dye, e.g., with a 5′ Cy3 label (the * in the scheme below). Upon deamination, excision, and cleavage of the strand, the substrate can be subjected to electrophoresis, and the substrate and any fragment released from it can be visualized by detecting the label. Where Cy5 is images, only the fragment with the label will be visible via imaging.


In one USER Enzyme assay, ssDNA substrates were used that matched the target sequences of the various deaminases tested. Expression cassettes encoding the deaminases tested were inserted into a CMV backbone plasmid that has been used previously in the lab (Addgene plasmid 52970). The deaminase proteins were expressed using a TNT Quick Coupled Transcription/Translation System (Promega) according to the manufacturers recommendations. After 90 min of incubation, 5 mL of lysate was incubated with 5′ Cy3-labeled ssDNA substrate and 1 unit of USER Enzyme (NEB) for 3 hours. The DNA was resolved on a 10% TBE PAGE gel and the DNA was imaged using Cy-dye imaging. A schematic representation of the USER Enzyme assay is shown in FIG. 41.



FIG. 1 shows the deaminase activity of the tested deaminases on ssDNA substrates, such as Doench 1, Doench 2, G7′ and VEGF Target 2. The rAPOBEC1 enzyme exhibited a substantial amount of deamination on the single-stranded DNA substrate with a canonical NGG PAM, but not with a negative control non-canonical NNN PAM. Cas9 fusion proteins with APOBEC family deaminases were generated. The following fusion architectures were constructed and tested on ssDNA:











rAPOBEC1-GGS-dCas9 primary sequence




(SEQ ID NO: 611)




MSSETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSIWRHTSQNT








NKHVEVNFIEKFTTERYFCPNTRCSITWFLSWSPCGECSRAITEFLSRYPHVTLFIYIAR







LYHHADPRNRQGLRDLISSGVTIQIMTEQESGYCWRNFVNYSPSNEAHWPRYPHLW








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rAPOBEC1-(GGS)3-dCas9 primary sequence



(SEQ ID NO: 612)




MSSETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSIWRHTSQNT








NKHVEVNFIEKFTTERYFCPNTRCSITWFLSWSPCGECSRAITEFLSRYPHVTLFIYIAR







LYHHADPRNRQGLRDLISSGVTIQIMTEQESGYCWRNFVNYSPSNEAHWPRYPHLW








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(SEQ ID NO: 613)





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VDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSIWRHTSQNTNKHVEVNFI







EKFTTERYFCPNTRCSITWFLSWSPCGECSRAITEFLSRYPHVTLFIYIARLYHHADPR







NRQGLRDLISSGVTIQIMTEQESGYCWRNFVNYSPSNEAHWPRYPHLWVRLYVLEL







YCIILGLPPCLNILRRKQPQLTFFTIALQSCHYQRLPPHILWATGLK








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(SEQ ID NO: 614)





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ETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSIWRHTSQNTNKH







VEVNFIEKFTTERYFCPNTRCSITWFLSWSPCGECSRAITEFLSRYPHVTLFIYIARLYH







HADPRNRQGLRDLISSGVTIQIMTEQESGYCWRNFVNYSPSNEAHWPRYPHLWVRL







YVLELYCIILGLPPCLNILRRKQPQLTFFTIALQSCHYQRLPPHILWATGLK








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(SEQ ID NO: 615)



MSSETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSIWRHTSQNT







NKHVEVNFIEKFTTERYFCPNTRCSITWFLSWSPCGECSRAITEFLSRYPHVTLFIYIAR







LYHHADPRNRQGLRDLISSGVTIQIMTEQESGYCWRNFVNYSPSNEAHWPRYPHLW








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FIG. 2 shows that the N-terminal deaminase fusions showed significant activity on the single stranded DNA substrates. For this reason, only the N-terminal architecture was chosen for further experiments.



FIG. 3 illustrates double stranded DNA substrate binding by deaminase-dCas9:sgRNA complexes. A number of double stranded deaminase substrate sequences were generated. The sequences are provided below. The structures according to FIG. 3 are identified in these sequences (36 bp: underlined, sgRNA target sequence: bold; PAM: boxed; 21 bp: italicized). All substrates were labeled with a 5′-Cy3 label:










(SEQ ID NO: 616)



2:GTAGGTAGTTAGGATGAATGGAAGGTTGGTATAGTCCCGCGGATTTATTTATTT





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(SEQ ID NO: 617)



3:GTAGGTAGTTAGGATGAATGGAAGGTTGGTATAGCTTCCGCGGATTTATTTATT





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(SEQ ID NO: 618)



4:GTAGGTAGTTAGGATGAATGGAAGGTTGGTATAGCCTTCCGCGGATTTATTTAT





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(SEQ ID NO: 619)



5:GTAGGTAGTTAGGATGAATGGAAGGTTGGTATAGCCATTCCGCGGATTTATTTA





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(SEQ ID NO: 620)



6:GTAGGTAGTTAGGATGAATGGAAGGTTGGTATAGCCTATTCCGCGGATTTATTT





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(SEQ ID NO: 621)



7:GTAGGTAGTTAGGATGAATGGAAGGTTGGTATAGCCTTATTCCGCGGATTTATT





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(SEQ ID NO: 622)



8:GTAGGTAGTTAGGATGAATGGAAGGTTGGTATAGCCATTATTCCGCGGATTTAT





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(SEQ ID NO: 623)



9:GTAGGTAGTTAGGATGAATGGAAGGTTGGTATAGCCTATTATTCCGCGGATTTA





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(SEQ ID NO: 624)



10:GTAGGTAGTTAGGATGAATGGAAGGTTGGTATAGCCATTATATTCCGCGGATTT





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(SEQ ID NO: 625)



11:GTAGGTAGTTAGGATGAATGGAAGGTTGGTATAGCCTATTATATTCCGCGGATT





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(SEQ ID NO: 626)



12:GTAGGTAGTTAGGATGAATGGAAGGTTGGTATAGCCTTATTATATTCCGCGGAT





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(SEQ ID NO: 627)



13:GTAGGTAGTTAGGATGAATGGAAGGTTGGTATAGCCATTATTATATTCCGCGGA





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(SEQ ID NO: 628)



14:GTAGGTAGTTAGGATGAATGGAAGGTTGGTATAGCCTATTATTATATTCCGCGG





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(SEQ ID NO: 629)



15:GTAGGTAGTTAGGATGAATGGAAGGTTGGTATAGCCATTATTATTATTACCGCG





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(SEQ ID NO: 630)



18:GTAGGTAGTTAGGATGAATGGAAGGTTGGTATAGCCATTATTATTATTATTACC





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“-”:


(SEQ ID NO: 631)




GTAGGTAGTTAGGATGAATGGAAGGTTGGTATAGTA
ATATTAATTTATTTATTTAA






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(SEQ ID NO: 632)



8U:GTAGGTAGTTAGGATGAATGGAAGGTTGGTGTAGATTATTATCUGCGGATTTA





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*In all substrates except for “8U”, the top strand in FIG. 3 is the complement of the sequence specified here. In the case of “8U”, there is a “G” opposite the U.



FIG. 4 shows the results of a double stranded DNA Deamination Assay. The fusions were expressed and purified with an N-terminal His6 tag via both Ni-NTA and sepharose chromatography. In order to assess deamination on dsDNA substrates, the various dsDNA substrates shown on the previous slide were incubated at a 1:8 dsDNA:fusion protein ratio and incubated at 37° C. for 2 hours. Once the dCas9 portion of the fusion binds to the DNA it blocks access of the USER enzyme to the DNA. Therefore, the fusion proteins were denatured following the incubation and the dsDNA was purified on a spin column, followed by incubation for 45 min with the USER Enzyme and resolution of the resulting DNA substrate and substrate fragments on a 10% TBE-urea gel.



FIG. 5 demonstrates that Cas9 fusions can target positions 3-11 of double-stranded DNA target sequences (numbered according to the schematic in FIG. 3). Upper Gel: 1 μM rAPOBEC1-GGS-dCas9, 125 nM dsDNA, 1 eq sgRNA. Mid Gel: 1 μM rAPOBEC1-(GGS)3-dCas9, 125 nM dsDNA, 1 eq sgRNA. Lower Gel: 1.85 μM rAPOBEC1-XTEN-dCas9, 125 nM dsDNA, 1 eq sgRNA. Based on the data from these gels, positions 3-11 (according to the numbering in FIG. 3) are sufficiently exposed to the activity of the deaminase to be targeted by the fusion proteins tested. Access of the deaminase to other positions is most likely blocked by the dCas9 protein.


The data further indicates that a linker of only 3 amino acids (GGS) is not optimal for allowing the deaminase to access the single stranded portion of the DNA. The 9 amino acid linker [(GGS)3] (SEQ ID NO: 596) and the more structured 16 amino acid linker (XTEN) allow for more efficient deamination.



FIG. 6 demonstrates that the correct guide RNA, e.g., the correct sgRNA, is required for deaminase activity. The gel shows that fusing the deaminase to dCas9, the deaminase enzyme becomes sequence specific (e.g., using the fusion with an eGFP sgRNA results in no deamination), and also confers the capacity to the deaminase to deaminate dsDNA. The native substrate of the deaminase enzyme is ssDNA, and no deamination occurred when no sgRNA was added. This is consistent with reported knowledge that APOBEC deaminase by itself does not deaminate dsDNA. The data indicates that Cas9 opens the double-stranded DNA helix within a short window, exposing single-stranded DNA that is then accessible to the APOBEC deaminase for cytidine deamination. The sgRNA sequences used are provided below. sequences (36 bp: underlined, sgRNA target sequence: bold; PAM: boxed; 21 bp: italicized) DNA sequence 8:










(SEQ ID NO: 633)



5′-Cy3-




GTAGGTAGTTAGGATGAATGGAAGGTTGGTATAGCC
ATTATTCCGCGGATTTATT





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Correct sgRNA sequence (partial 3′ sequence):


(SEQ ID NO: 634)



5′-AUUAUUCCGCGGAUUUAUUUGUUUUAGAGCUAG...-3′






eGFP sgRNA sequence (partial 3′-sequence):


(SEQ ID NO: 635)



5′-CGUAGGCCAGGGUGGUCACGGUUUUAGAGCUAG...-3′







Example 2: Deamination of DNA Target Sequence

Exemplary deamination targets. The dCas9:deaminase fusion proteins described herein can be delivered to a cell in vitro or ex vivo or to a subject in vivo and can be used to effect C to T or G to A transitions when the target nucleotide is in positions 3-11 with respect to a PAM. Exemplary deamination targets include, without limitation, the following: CCR5 truncations: any of the codons encoding Q93, Q102, Q186, R225, W86, or Q261 of CCR5 can be deaminated to generate a STOP codon, which results in a nonfunctional truncation of CCR5 with applications in HIV treatment. APOE4 mutations: mutant codons encoding C11R and C57R mutant APOE4 proteins can be deaminated to revert to the wild-type amino acid with applications in Alzheimer's treatment. eGFP truncations: any of the codons encoding Q158, Q184, Q185 can be deaminated to generate a STOP codon, or the codon encoding M1 can be deaminated to encode I, all of which result in loss of eGFP fluorescence, with applications in reporter systems. eGFP restoration: a mutant codon encoding T65A or Y66C mutant GFP, which does not exhibit substantial fluorescence, can be deaminated to restore the wild-type amino acid and confer fluorescence. PIK3CA mutation: a mutant codon encoding K111E mutant PIK3CA can be deaminated to restore the wild-type amino acid residue with applications in cancer. CTNNB1 mutation: a mutant codon encoding T41A mutant CTNNB1 can be deaminated to restore the wild-type amino acid residue with applications in cancer. HRAS mutation: a mutant codon encoding Q61R mutant HRAS can be deaminated to restore the wild-type amino acid residue with applications in cancer. P53 mutations: any of the mutant codons encoding Y163C, Y236C, or N239D mutant p53 can be deaminated to encode the wild type amino acid sequence with applications in cancer. The feasibility of deaminating these target sequences in double-stranded DNA is demonstrated in FIGS. 7 and 8. FIG. 7 illustrates the mechanism of target DNA binding of in vivo target sequences by deaminase-dCas9:sgRNA complexes.



FIG. 8 shows successful deamination of exemplary disease-associated target sequences. Upper Gel: CCR5 Q93: coding strand target in pos. 10 (potential off-targets at positions 2, 5, 6, 8, 9); CCR5 Q102: coding strand target in pos. 9 (potential off-targets at positions 1, 12, 14); CCR5 Q186: coding strand target in pos. 9 (potential off-targets at positions 1, 5, 15); CCR5 R225: coding strand target in pos. 6 (no potential off-targets); eGFP Q158: coding strand target in pos. 5 (potential off-targets at positions 1, 13, 16); eGFP Q184/185: coding strand target in pos. 4 and 7 (potential off-targets at positions 3, 12, 14, 15, 16, 17, 18); eGFP M1: template strand target in pos. 12 (potential off-targets at positions 2, 3, 7, 9, 11) (targets positions 7 and 9 to small degree); eGFP T65A: template strand target in pos. 7 (potential off-targets at positions 1, 8, 17); PIK3CA K111E: template strand target in pos. 2 (potential off-targets at positions 5, 8, 10, 16, 17); PIK3CA K111E: template strand target in pos. 13 (potential off-targets at positions 11, 16, 19) X. Lower Gel: CCR5 W86: template strand target in pos. 2 and 3 (potential off-targets at positions 1, 13) X; APOE4 C11R: coding strand target in pos. 11 (potential off-targets at positions 7, 13, 16, 17); APOE4 C57R: coding strand target in pos. 5) (potential off-targets at positions 7, 8, 12); eGFP Y66C: template strand target in pos. 11 (potential off-targets at positions 1, 4, 6, 8, 9, 16); eGFP Y66C: template strand target in pos. 3 (potential off-targets at positions 1, 8, 17); CCR5 Q261: coding strand target in pos. 10 (potential off-targets at positions 3, 5, 6, 9, 18); CTNNB1 T41A: template strand target in pos. 7 (potential off-targets at positions 1, 13, 15, 16) X; HRAS Q61R: template strand target in pos. 6 (potential off-targets at positions 1, 2, 4, 5, 9, 10, 13); p53 Y163C: template strand target in pos. 6 (potential off-targets at positions 2, 13, 14); p53 Y236C: template strand target in pos. 8 (potential off-targets at positions 2, 4); p53 N239D: template strand target in pos. 4 (potential off-targets at positions 6, 8). Exemplary DNA sequences of disease targets are provided below (PAMs (5′-NGG-3′) and target positions are boxed):









(SEQ ID NO: 636)


CCR5 Q93: 5′-Cy3-



GTAGGTAGTTAGGATGAATGGAAGGTTGGTAACTAT
GCTGCCGCC





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(SEQ ID NO: 637)


CCR5 Q102: 5′-Cy3-



GTAGGTAGTTAGGATGAATGGAAGGTTGGTAAAATA
CAATGTGT





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(SEQ ID NO: 638)


CCR5 Q186: 5'-Cy3-



GTAGGTAGTTAGGATGAATGGAAGGTTGGTATTTTC
CATACAGT





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(SEQ ID NO: 639)


CCR5 R225: 5′-Cy3-




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(SEQ ID NO: 640)


CCR5 W86: 5′-Cy3-




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(SEQ ID NO: 641)


CCR5 Q261: 5′-Cy3-



GTAGGTAGTTAGGATGAATGGAAGGTTGGTATCCTG
AACACCTT





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(SEQ ID NO: 642)


APOE4 C11R: 5′-Cy3-



GTAGGTAGTTAGGATGAATGGAAGGTTGGTAGACAT
GGAGGAC





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(SEQ ID NO: 643)


APOE4 C57R: 5′-Cy3-




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(SEQ ID NO: 644)


eGFP Q158: 5′-Cy3-




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(SEQ ID NO: 645)


eGFP Q184/185: 5′-Cy3-




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(SEQ ID NO: 646)


eGFP M1: 5′-Cy3-



GTAGGTAGTTAGGATGAATGGAAGGTTGGTACCTCG
CCCTTGCTCA





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(SEQ ID NO: 647)


eGFP T65A: 5′-Cy3-




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(SEQ ID NO: 648)


eGFP Y66C: 5'-Cy3-



GTAGGTAGTTAGGATGAATGGAAGGTTGGTAAAGCA
CTGCACTC





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(SEQ ID NO: 649)


eGFP Y66C: 5′-Cy3-




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(SEQ ID NO: 650)


P1K3CA K111E: 5′-Cy3-




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(SEQ ID NO: 651)


P1K3CA K111E: 5′-Cy3-



GTAGGTAGTTAGGATGAATGGAAGGTTGGTATTCTC
GATTG





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(SEQ ID NO: 652)


CTNNB1 T41A: 5′-Cy3-



GTAGGTAGTTAGGATGAATGGAAGGTTGGTAAGGAG
CTGTGG





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(SEQ ID NO: 653)


HRAS Q61R: 5′-Cy3-




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(SEQ ID NO: 654)


p53 Y163C: 5′-Cy3-




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(SEQ ID NO: 655)


p53 Y236C: 5′-Cy3-




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(SEQ ID NO: 656)


p53 N239D: 5′-Cy3-




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Example 3: Uracil Glycosylase Inhibitor Fusion Improves Deamination Efficiency

Direct programmable nucleobase editing efficiencies in mammalian cells by dCas9:deaminase fusion proteins can be improved significantly by fusing a uracil glycosylase inhibitor (UGI) to the dCas9:deaminase fusion protein.



FIG. 9 shows in vitro C→T editing efficiencies in human HEK293 cells using rAPOBEC1-XTEN-dCas9:












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(SEQ ID NO: 657)




MSSETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSIWRHTSQNT








NKHVEVNFIEKFTTERYFCPNTRCSITWFLSWSPCGECSRAITEFLSRYPHVTLFIYIAR







LYHHADPRNRQGLRDLISSGVTIQIMTEQESGYCWRNFVNYSPSNEAHWPRYPHLWV







RLYVLELYCIILGLPPCLNILRRKQPQLTFFTIALQSCHYQRLPPHILWATGLK
SGSETP








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KV

















EMX1:


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(SEQ ID NO: 293)






FANCF:


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(SEQ ID NO: 294)





HEK293 site 2:


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(SEQ ID NO: 295)





HEK293 site 3:


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(SEQ ID NO: 296)





HEK293 site 4:


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(SEQ ID NO: 297)





RNF2:


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(SEQ ID NO: 298)







*PAMs are boxed, C residues within target window (positions 3-11) are numbered and bolded.



FIG. 10 demonstrates that C→T editing efficiencies on the same protospacer sequences in HEK293T cells are greatly enhanced when a UGI domain is fused to the rAPOBEC1:dCas9 fusion protein.












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(SEQ ID NO: 658)




MSSETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSIWRHTSQNT








NKHVEVNFIEKFTTERYFCPNTRCSITWFLSWSPCGECSRAITEFLSRYPHVTLFIYIAR







LYHHADPRNRQGLRDLISSGVTIQIMTEQESGYCWRNFVNYSPSNEAHWPRYPHLWV







RLYVLELYCIILGLPPCLNILRRKQPQLTFFTIALQSCHYQRLPPHILWATGLK
SGSETP








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IIEKETGKOLVICIESILMLPEEVEEVIGNKPESDILVHTAYDESTDENVMLLTSDAP









EYKPWALVICIDSNGENKIKML

SGGSPKKKRKV







The percentages in FIGS. 9 and 10 are shown from sequencing both strands of the target sequence. Because only one of the strands is a substrate for deamination, the maximum possible deamination value in this assay is 50%. Accordingly, the deamination efficiency is double the percentages shown in the tables. E.g., a value of 50% relates to deamination of 100% of double-stranded target sequences.


When a uracil glycosylase inhibitor (UGI) was fused to the dCas9:deaminase fusion protein (e.g., rAPOBEC1-XTEN-dCas9-[UGI]-NLS), a significant increase in editing efficiency in cells was observed. This result indicates that in mammalian cells, the DNA repair machinery that cuts out the uracil base in a U:G base pair is a rate-limiting process in DNA editing. Tethering UGI to the dVas9:deaminase fusion proteins greatly increases editing yields.


Without UGI, typical editing efficiencies in human cells were in the ˜2-14% yield range (FIG. 9 and FIG. 10, “XTEN” entries). With UGI (FIG. 10, “UGI” entries) the editing was observed in the ˜6-40% range. Using a UGI fusion is thus more efficient than the current alternative method of correcting point mutations via HDR, which also creates an excess of indels in addition to correcting the point mutation. No indels resulting from treatment with the cas9:deaminase:UGI fusions were observed.


Example 4: Direct, Programmable Conversion of a Target Nucleotide in Genomic DNA without Double-Stranded DNA Cleavage

Current genome-editing technologies introduce double-stranded DNA breaks at a target locus of interest as the first step to gene correction.39,40 Although most genetic diseases arise from mutation of a single nucleobase to a different nucleobase, current approaches to revert such changes are very inefficient and typically induce an abundance of random insertions and deletions (indels) at the target locus as a consequence of the cellular response to double-stranded DNA breaks.39,40 Reported herein is the development of nucleobase editing, a new strategy for genome editing that enables the direct conversion of one target nucleobase into another in a programmable manner, without requiring double-stranded DNA backbone cleavage. Fusions of CRISPR/Cas9 were engineered and the cytidine deaminase enzyme APOBEC1 that retain the ability to be programmed with a guide RNA, do not induce double-stranded DNA breaks, and mediate the direct conversion of cytidine to uracil, thereby effecting a C→T (or G→A) substitution following DNA replication, DNA repair, or transcription if the template strand is targeted. The resulting “nucleobase editors” convert cytidines within a window of approximately five nucleotides, and can efficiently correct a variety of point mutations relevant to human disease in vitro. In four transformed human and murine cell lines, second- and third-generation nucleobase editors that fuse uracil glycosylase inhibitor (UGI), and that use a Cas9 nickase targeting the non-edited strand, respectively, can overcome the cellular DNA repair response to nucleobase editing, resulting in permanent correction of up to 37% or (˜15-75%) of total cellular DNA in human cells with minimal (typically ≤1%) indel formation. In contrast, canonical Cas9-mediated HDR on the same targets yielded an average of 0.7% correction with 4% indel formation. Nucleobase editors were used to revert two oncogenic p53 mutations into wild-type alleles in human breast cancer and lymphoma cells, and to convert an Alzheimer's Disease associated Arg codon in ApoE4 into a non-disease-associated Cys codon in mouse astrocytes. Base editing expands the scope and efficiency of genome editing of point mutations.


The clustered regularly interspaced short palindromic repeat (CRISPR) system is a prokaryotic adaptive immune system that has been adapted to mediate genome engineering in a variety of organisms and cell lines.41 CRISPR/Cas9 protein-RNA complexes localize to a target DNA sequence through base pairing with a guide RNA, and natively create a DNA double-stranded break (DSB) at the locus specified by the guide RNA. In response to DSBs, endogenous DNA repair processes mostly result in random insertions or deletions (indels) at the site of DNA cleavage through non-homologous end joining (NHEJ). In the presence of a homologous DNA template, the DNA surrounding the cleavage site can be replaced through homology-directed repair (HDR). When simple disruption of a disease-associated gene is sufficient (for example, to treat some gain-of-function diseases), targeted DNA cleavage followed by indel formation can be effective. For most known genetic diseases, however, correction of a point mutation in the target locus, rather than stochastic disruption of the gene, is needed to address or study the underlying cause of the disease.68


Motivated by this need, researchers have invested intense effort to increase the efficiency of HDR and suppress NHEJ. For example, a small-molecule inhibitor of ligase IV, an essential enzyme in the NHEJ pathway, has been shown to increase HDR efficiency.42,43 However, this strategy is challenging in post-mitotic cells, which typically down-regulate HDR, and its therapeutic relevance is limited by the potential risks of inhibiting ligase IV in non-target cells. Enhanced HDR efficiency can also be achieved by the timed delivery of Cas9-guide RNA complexes into chemically synchronized cells, as HDR efficiency is highly cell-cycle dependent.44 Such an approach, however, is limited to research applications in cell culture since synchronizing cells is highly disruptive. Despite these developments, current strategies to replace point mutations using HDR in most contexts are very inefficient (typically ˜0.1 to 5%),42,43,45,46,75 especially in unmodified, non-dividing cells. In addition, HDR competes with NHEJ during the resolution of double-stranded breaks, and indels are generally more abundant outcomes than gene replacement. These observations highlight the need to develop alternative approaches to install specific modifications in genomic DNA that do not rely on creating double-stranded DNA breaks. A small-molecule inhibitor of ligase IV, an essential enzyme in the NHEJ pathway, has been shown to increase HDR efficiency.42,43 However, this strategy is challenging in post-mitotic cells, which typically down-regulate HDR, and its therapeutic relevance is limited by the potential risks of inhibiting ligase IV in non-target cells. Enhanced HDR efficiency can also be achieved by the timed delivery of Cas9-guide RNA complexes into chemically synchronized cells, as HDR efficiency is highly cell-cycle dependent.44 Such an approach, however, is limited to research applications in cell culture since synchronizing cells is highly disruptive. In some cases, it is possible to design HDR templates such that the product of successful HDR contains mutations in the PAM sequence and therefore is no longer a substrate for subsequent Cas9 modification, increasing the overall yield of HDR products,75 although such an approach imposes constraints on the product sequences. Recently, this strategy has been coupled to the use of ssDNA donors that are complementary to the non-target strand and high-efficiency ribonucleoprotein (RNP) delivery to substantially increase the efficiency of HDR, but even in these cases the ratio of HDR to NHEJ outcomes is relatively low (<2).83


It was envisioned that direct catalysis of the conversion of one nucleobase to another at a programmable target locus without requiring DNA backbone cleavage could increase the efficiency of gene correction relative to HDR without introducing undesired random indels at the locus of interest. Catalytically dead Cas9 (dCas9), which contains Asp10Ala and His840Ala mutations that inactivate its nuclease activity, retains its ability to bind DNA in a guide RNA-programmed manner but does not cleave the DNA backbone.16,47 In principle, conjugation of dCas9 with an enzymatic or chemical catalyst that mediates the direct conversion of one nucleobase to another could enable RNA-programmed nucleobase editing. The deamination of cytosine (C) is catalyzed by cytidine deaminases29 and results in uracil (U), which has the base pairing properties of thymine (T). dCas9 was fused to cytidine deaminase enzymes in order to test their ability to convert C to U at a guide RNA-specified DNA locus. Most known cytidine deaminases operate on RNA, and the few examples that are known to accept DNA require single-stranded DNA.48 Recent studies on the dCas9-target DNA complex reveal that at least nine nucleotides of the displaced DNA strand are unpaired upon formation of the Cas9:guide RNA:DNA “R-loop” complex.12 Indeed, in the structure of the Cas9R-loop complex the first 11 nucleotides of the protospacer on the displaced DNA strand are disordered, suggesting that their movement is not highly restricted.76It has also been speculated that Cas9 nickase-induced mutations at cytosines in the non-template strand might arise from their accessibility by cellular cytidine deaminase enzymes.77 Recent studies on the dCas9-target DNA complex have revealed that at least 26 bases on the non-template strand are unpaired when Cas9 binds to its target DNA sequence.49 It was reasoned that a subset of this stretch of single-stranded DNA in the R-loop might serve as a substrate for a dCas9-tethered cytidine deaminase to effect direct, programmable conversion of C to U in DNA (FIG. 11A).


Four different cytidine deaminase enzymes (hAID, hAPOBEC3G, rAPOBEC1, and pmCDA1) were expressed in a mammalian cell lysate-derived in vitro transcription-translation system and evaluated for ssDNA deamination. Of the four enzymes, rAPOBEC1 showed the highest deaminase activity under the tested conditions and was chosen for dCas9 fusion experiments (FIG. 36A). Although appending rAPOBEC1 to the C-terminus of dCas9 abolishes deaminase activity, fusion to the N-terminus of dCas9 preserves deaminase activity on ssDNA at a level comparable to that of the unfused enzyme. Four rAPOBEC1-dCas9 fusions were expressed and purified with linkers of different length and composition (FIG. 36B), and evaluated each fusion for single guide RNA (sgRNA)-programmed dsDNA deamination in vitro (FIGS. 11A to 11C and FIGS. 15A to 15D).


Efficient, sequence-specific, sgRNA-dependent C to U conversion was observed in vitro (FIGS. 11A to 11C). Conversion efficiency was greatest using rAPOBEC1-dCas9 linkers over nine amino acids in length. The number of positions susceptible to deamination (the deamination “activity window”) increases with linker length was extended from three to 21 amino acids (FIGS. 36C to 36F15A to 15D). The 16-residue XTEN linker50 was found to offer a promising balance between these two characteristics, with an efficient deamination window of approximately five nucleotides, from positions 4 to 8 within the protospacer, counting the end distal to the protospacer-adjacent motif (PAM) as position 1. The rAPOBEC1-XTEN-dCas9 protein served as the first-generation nucleobase editor (NBE1).


Elected were seven mutations relevant to human disease that in theory could be corrected by C to T nucleobase editing, synthesized double-stranded DNA 80-mers of the corresponding sequences, and assessed the ability of NBE1 to correct these mutations in vitro (FIGS. 16A to 16B). NBE1 yielded products consistent with efficient editing of the target C, or of at least one C within the activity window when multiple Cs were present, in six of these seven targets in vitro, with an average apparent editing efficiency of 44% (FIGS. 16A to 16B). In the three cases in which multiple Cs were present within the deamination window, evidence of deamination of some or all of these cytosines was observed. In only one of the seven cases tested were substantial yields of edited product observed (FIGS. 16A to 16B).


Although the preferred sequence context for APOBEC1 substrates is reported to be CC or TC,51 it was anticipated that the increased effective molarity of the deaminase and its single-stranded DNA substrate mediated by dCas9 binding to the target locus may relax this restriction. To illuminate the sequence context generality of NBE1, its ability to edit a 60-mer double-stranded DNA oligonucleotide containing a single fixed C at position 7 within the protospacer was assayed, as well as all 36 singly mutated variants in which protospacer bases 1-6 and 8-13 were individually varied to each of the other three bases. Each of these 37 sequences were treated with 1.9 μM NBE1, 1.9 μM of the corresponding sgRNA, and 125 nM DNA for 2 h, similar to standard conditions for in vitro Cas9 assays52. High-throughput DNA sequencing (HTS) revealed 50 to 80% C to U conversion of targeted strands (25 to 40% of total sequence reads arising from both DNA strands, one of which is not a substrate for NBE1) (FIG. 12A). The nucleotides surrounding the target C had little effect on editing efficiency was independent of sequence context unless the base immediately 5′ of the target C is a G, in which case editing efficiency was substantially lower (FIGS. 12A to 12B). NBE1 activity in vitro was assessed on all four NC motifs at positions 1 through 8 within the protospacer (FIGS. 12A to 12B). In general NBE1 activity on substrates was observed to follow the order TC≥CC≥AC>GC, with maximum editing efficiency achieved when the target C is at or near position 7. In addition, it was observed that the nucleobase editor is highly processive, and will efficiently convert most of all Cs to Us on the same DNA strand within the 5-base activity window (FIG. 17).


While BE1 efficiently processes substrates in a test tube, in cells a tree of possible DNA repair outcomes determines the fate of the initial U:G product of base editing (FIG. 29A). To test the effectiveness of nucleobase editing in human cells, NBE1 codon usage was optimized for mammalian expression, appended a C-terminal nuclear localization sequence (NLS),53 and assayed its ability to convert C to T in human cells on 14Cs in six well-studied target sites throughout the human genome (FIG. 37A).54 The editable Cs were confirmed within each protospacer in vitro by incubating NBE1 with synthetic 80-mers that correspond to the six different genomic sites, followed by HTS (FIGS. 13A to 13C, FIG. 29B and FIG. 25). Next, HEK293T cells were transfected with plasmids encoding NBE1 and one of the six target sgRNAs, allowed three days for nucleobase editing to occur, extracted genomic DNA from the cells, and analyzed the loci by HTS. Although C to T editing in cells at the target locus was observed for all six cases, the efficiency of nucleobase editing was 1.1% to 6.3% or 0.8%-7.7% of total DNA sequences (corresponding to 2.2% to 12.6% of targeted strands), a 6.3-fold to 37-fold or 5-fold to 36-fold decrease in efficiency compared to that of in vitro nucleobase editing (FIGS. 13A to 13C, FIG. 29B and FIG. 25). It was observed that some base editing outside of the typical window of positions 4 to 8 when the substrate C is preceded by a T, which we attribute to the unusually high activity of APOBEC1 for TC substrates.48


It was asked whether the cellular DNA repair response to the presence of U:G heteroduplex DNA was responsible for the large decrease in nucleobase editing efficiency in cells (FIG. 29A). Uracil DNA glycosylase (UDG) catalyzes removal of U from DNA in cells and initiates base excision repair (BER), with reversion of the U:G pair to a C:G pair as the most common outcome (FIG. 29A).55 Uracil DNA glycosylase inhibitor (UGI), an 83-residue protein from B. subtilis bacteriophage PBS1, potently blocks human UDG activity (IC50=12 μM).56 UGI was fused to the C-terminus of NBE1 to create the second-generation nucleobase editor NBE2 and repeated editing assays on all six genomic loci. Editing efficiencies in human cells were on average 3-fold higher with NBE2 than with NBE1, resulting in gene conversion efficiencies of up to 22.8% of total DNA sequenced (up to 45.6% of targeted strands) (FIGS. 13A to 13C and FIG. 29B). To test base editing in human cells, BE1 codon usage was optimized for mammalian expression and appended a C-terminal nuclear localization sequence (NLS).53


Similar editing efficiencies were observed when a separate plasmid overexpressing UGI was co-transfected with NBE1 (FIGS. 18A to 18H). However, while the direct fusion of UGI to NBE1 resulted in no significant increase in C to T mutations at monitored non-targeted genomic locations, overexpression of unfused UGI detectably increased the frequency of C to T mutations elsewhere in the genome (FIGS. 18A to 18H). The generality of NBE2-mediated nucleobase editing was confirmed by assessing editing efficiencies on the same six genomic targets in U2OS cells, and observed similar results with those in HEK293T cells (FIG. 19). Importantly, NBE2 typically did not result in any detectable indels (FIG. 13C and FIG. 29C), consistent with the known mechanistic dependence of NHEJ on double-stranded DNA breaks.57,78 Together, these results indicate that conjugating UGI to NBE1 can greatly increase the efficiency of nucleobase editing in human cells.


The permanence of nucleobase editing in human cells was confirmed by monitoring editing efficiencies over multiple cell divisions in HEK293T cells at two of the tested genomic loci. Genomic DNA was harvested at two time points: three days after transfection with plasmids expressing NBE2 and appropriate sgRNAs, and after passaging the cells and growing them for four additional days (approximately five subsequent cell divisions). No significant change in editing efficiency was observed between the non-passaged cells (editing observed in 4.6% to 6.6% of targeted strands for three different target Cs) and passaged cells (editing observed in 4.6% to 6.4% of targeted strands for the same three target Cs), confirming that the nucleobase edits became permanent following cell division (FIG. 20). Indels will on rare occasion arise from the processing of U:G lesions by cellular repair processes, which involve single-strand break intermediates that are known to lead to indels.84 Given that several hundred endogenous U:G lesions are generated every day per human cell from spontaneous cytidine deaminase,85 it was anticipate that the total indel frequency from U:G lesion repair is unlikely to increase from BE1 or BE2 activity at a single target locus.


To further increase the efficiency of nucleobase editing in cells, it was anticipated that nicking the non-edited strand may result in a smaller fraction of edited Us being removed by the cell, since eukaryotic mismatch repair machinery uses strand discontinuity to direct DNA repair to any broken strand of a mismatched duplex (FIG. 29A).58, 79, 80 The catalytic His residue was restored at position 840 in the Cas9 HNH domain,47,59 resulting in the third-generation nucleobase editor NBE3 that nicks the non-edited strand containing a G opposite the targeted C, but does not cleave the target strand containing the C. Because NBE3 still contains the Asp10A1a mutation in Cas9, it does not induce double-stranded DNA cleavage. This strategy of nicking the non-edited strand augmented nucleobase editing efficiency in human cells by an additional 1.4- to 4.8-fold relative to NBE2, resulting in up to 36.3% of total DNA sequences containing the targeted C to T conversion on the same six human genomic targets in HEK293T cells (FIGS. 13A to 13C and FIG. 29B). Importantly, only a small frequency of indels, averaging 0.8% (ranging from 0.2% to 1.6% for the six different loci), was observed from NBE3 treatment (FIG. 13C, FIG. 29C, and FIG. 34). In contrast, when cells were treated with wild-type Cas9, sgRNA, and a single-stranded DNA donor template to mediate HDR at three of these loci C to T conversion efficiencies averaging only 0.7% were observed, with much higher relative indel formation averaging 3.9% (FIGS. 13A to 13C and FIG. 29C). The ratio of allele conversion to NHEJ outcomes averaged >1,000 for BE2, 23 for BE3, and 0.17 for wild-type Cas9 (FIG. 3c). We confirmed the permanence of base editing in human cells by monitoring editing efficiencies over multiple cell divisions in HEK293T cells at the HEK293 site 3 and 4 genomic loci (FIG. 38). These results collectively establish that nucleobase editing can effect much more efficient targeted single-base editing in human cells than Cas9-mediated HDR, and with much less (NBE3) or no (NBE2) indel formation.


Next, the off-target activity of NBE1, NBE2, and NBE3 in human cells was evaluated. The off-target activities of Cas9, dCas9, and Cas9 nickase have been extensively studied (FIGS. 23 to 24 and 31 to 33).54,60-62 Because the sequence preference of rAPOBEC1 has been shown to be independent of DNA bases more than one base from the target C,63 consistent with the sequence context independence observed in FIGS. 12A to 12B, it was assumed that potential off-target activity of nucleobase editors arises from off-target Cas9 binding. Since only a fraction of Cas9 off-target sites will have a C within the active window for nucleobase editing, off-target nucleobase editing sites should be a subset of the off-target sites of canonical Cas9 variants. For each of the six sites studied, the top ten known Cas9 off-target loci in human cells that were previously determined using the GUIDE-seq method were sequenced (FIGS. 23 to 27 and 31 to 33).54, 61 Detectable off-target nucleobase editing at only a subset (16/34, 47% for NBE1 and NBE2, and 17/34, 50% for NBE3) of known dCas9 off-target loci was observed. In all cases, the off-target base-editing substrates contained a C within the five-base target window. In general, off-target C to T conversion paralleled off-target Cas9 nuclease-mediated genome modification frequencies (FIGS. 23 to 27). Also monitored were C to T conversions at 2,500 distinct cytosines surrounding the six on-target and 34 off-target loci tested, representing a total of 14,700,000 sequence reads derived from approximately 1.8×106 cells, and observed no detectable increase in C to T conversions at any of these other sites upon NBE1, NBE2, or NBE3 treatment compared to that of untreated cells (FIG. 28). Taken together, these findings suggest that off-target substrates of nucleobase editors include a subset of Cas9 off-target substrates, and that nucleobase editors in human cells do not induce untargeted C to T conversion throughout the genome at levels that can be detected by the methods used here. No substantial change was observed in editing efficiency between non-passaged HEK293T cells (editing observed in 1.8% to 2.6% of sequenced strands for the three target Cs with BE2, and 6.2% to 14.3% with BE3) and cells that had undergone approximately five cell divisions after base editing (editing observed in 1.9% to 2.3% of sequenced strands for the same target Cs with BE2, and 6.4% to 14.5% with BE3), confirming that base edits in these cells are durable (Extended Data FIG. 6).


Finally, the potential of nucleobase editing to correct three disease-relevant mutations in mammalian cells was tested. The apolipoprotein E gene variant APOE4 encodes two Arg residues at amino acid positions 112 and 158, and is the largest and most common genetic risk factor for late-onset Alzheimer's disease.64 ApoE variants with Cys residues in positions 112 or 158, including APOE2 (Cys112/Cys158), APOE3 (Cys112/Arg158), and APOE3′ (Arg112/Cys158) have been shown65 or are presumed81 to confer substantially lower Alzheimer's disease risk than APOE4. Encouraged by the ability of NBE1 to convert APOE4 to APOE3′ in vitro (FIGS. 16A to 16B), this conversion was attempted in immortalized mouse astrocytes in which the endogenous murine APOE gene has been replaced by human APOE4 (Taconic). DNA encoding NBE3 and an appropriate sgRNA was delivered into these astrocytes by nucleofection (nucleofection efficiency of 25%), extracted genomic DNA from all treated cells two days later, and measured editing efficiency by HTS. Conversion of Arg158 to Cys158 was observed in 58-75% of total DNA sequencing reads (44% of nucleofected astrocytes) (FIGS. 14A to 14C and FIGS. 30A). Also observed was 36-50% editing of total DNA at the third position of codon 158 and 38-55% editing of total DNA at the first position of Leu159, as expected since all three of these Cs are within the active nucleobase editing window. However, neither of the other two C→T conversions results in a change in the amino acid sequence of the ApoE3′ protein since both TGC and TGT encode Cys, and both CTG and TTG encode Leu. From >1,500,000 sequencing reads derived from 1×106 cells evidence of 1.7% indels at the targeted locus following NBE3 treatment was observed (FIG. 35). In contrast, identical treatment of astrocytes with wt Cas9 and donor ssDNA resulted in 0.1-0.3% APOE4 correction and 26-40% indels at the targeted locus, efficiencies consistent with previous reports of single-base correction using Cas9 and HDR45,75 (FIG. 30A and FIG. 40A). Astrocytes treated identically but with an sgRNA targeting the VEGFA locus displayed no evidence of APOE4 base editing (FIG. 34 and FIG. 40A). These results demonstrate how nucleobase editors can effect precise, single-amino acid changes in the coding sequence of a protein as the major product of editing, even when their processivity results in more than one nucleotide change in genomic DNA. The off-target activities of Cas9, dCas9, and Cas9 nickase have been extensively studied.54, 60-62 In general, off-target C to T conversions by BE1, BE2, and BE3 paralleled off-target Cas9 nuclease-mediated genome modification frequencies.


The dominant-negative p53 mutations Tyr163Cys and Asn239Asp are strongly associated with several types of cancer.66-67 Both of these mutations can be corrected by a C to T conversion on the template strand (FIGS. 16A to 16B). A human breast cancer cell line homozygous for the p53 Tyr163Cys mutation (HCC1954 cells) was nucleofected with DNA encoding NBE3 and an sgRNA programmed to correct Tyr163Cys. Because the nucleofection efficiency of HCC1954 cells was <10%, a plasmid expressing IRFP was co-nucleofected into these cells to enable isolation of nucleofected cells by fluorescence-activated cell sorting two days after treatment. HTS of genomic DNA revealed correction of the Tyr163Cys mutation in 7.6% of nucleofected HCC1954 cells (FIG. 30B and FIG. 40A to 40B). Also nucleofected was a human lymphoma cell line that is heterozygous for p53 Asn239Asp (ST486 cells) with DNA encoding NBE2 and an sgRNA programmed to correct Asn239Asp with 92% nucleofection efficiency). Correction of the Asn239Asp mutation was observed in 11% of treated ST486 cells (12% of nucleofected ST486 cells). Consistent with the findings in HEK cells, no indels were observed from the treatment of ST486 cells with NBE2, and 0.6% indel formation from the treatment of HCC1954 cells with NBE3. No other DNA changes within at least 50 base pairs of both sides of the protospacer were detected at frequencies above that of untreated controls out of >2,000,000 sequencing reads derived from 2×105 cells (FIGS. 14A to 14C, FIG. 30B and Table 1). These results collectively represent the conversion of three disease-associated alleles in genomic DNA into their wild-type forms with an efficiency and lack of other genome modification events that is, to our knowledge, not currently achievable using other methods.


To illuminate the potential relevance of nucleobase editors to address human genetic diseases, the NCBI ClinVar database68 was searched for known genetic diseases that could in principle be corrected by this approach. ClinVar was filtered by first examining only single nucleotide polymorphisms (SNPs), then removing any nonpathogenic variants. Out of the 24,670 pathogenic SNPs, 3,956 are caused by either a T to C, or an A to G, substitution. This list was further filtered to only include variants with a nearby NGG PAM that would position the SNP within the deamination activity window, resulting in 1,089 clinically relevant pathogenic gene variants that could in principle be corrected by the nucleobase editors described here (FIG. 21 and Table 1). To illuminate the potential relevance of base editors to address human genetic diseases, the NCBI ClinVar database68 was searched for known genetic diseases that could in principle be corrected by this approach. ClinVar was filtered by first examining only single nucleotide polymorphisms (SNPs), then removing any non-pathogenic variants. Out of the 24,670 pathogenic SNPs, 3,956 are caused by either a T to C, or an A to G, substitution. This list was further filtered to only include variants with a nearby NGG PAM that would position the SNP within the deamination activity window, resulting in 911 clinically relevant pathogenic gene variants that could in principle be corrected by the base editors described here. Of these, 284 contain only one C within the base editing activity window. A detailed list of these pathogenic mutations can be found in Table 1.









TABLE 1







List of 911 base-editable gene variants associated with human disease


with an NGG PAM (SEQ ID NOs: 747 to 1868 appear from top to bottom below,


respectively). The “Y” in the protospacer and PAM sequences indicates the base to be edited,


e.g., C. (SEQ ID NOs: 747 to 1868 appear from top to bottom below, respectively)












Protospacer



dbSNP #
Genotype
and PAM sequence(s)
Associated genetic disease













755445790
NM_000391.3(TPP1):c.887-10A>G
TTTYTTTTTTTTTTTTTTTGAGG
Ceroid lipofuscinosis, neuronal, 2





113994167
NM_000018.3(ACADVL):c.848T>C
TTTGYGGTGGAGAGGGGCTTCGG,
Very long chain acyl-CoA



(p.Val283Ala)
TTGYGGTGGAGAGGGGCTTCGGG
dehydrogenase deficiency





119470018
NM_024996.5(GFM1):c.521A>G
TTGYTAATAAAAGTTAGAAACGG
Combined oxidative phosphorylation



(p.Asn174Ser)

deficiency 1





115650537
NM_000426.3(LAMA2):c.8282T>C
TTGAYAGGGAGCAAGCAGTTCGG,
Merosin deficient congenital



(p.Ile2761Thr)
TGAYAGGGAGCAAGCAGTTCGGG
muscular dystrophy





587777752
NM_014946.3(SPAST):c.1688-
TTCYGTAAAACATAAAAGTCAGG
Spastic paraplegia 4, autosomal dominant





794726821
NM_001165963.1(SCN1A):c.4055T>C
TTCYGGTTTGTCTTATATTCTGG
Severe myoclonic epilepsy in infancy



(p.Leu1352Pro)







397514745
NM_001130089.1(KARS):c.517T>C
CTTCYATGATCTTCGAGGAGAGG,
Deafness, autosomal recessive 89



(p.Tyr173His)
TTCYATGATCTTCGAGGAGAGG





G






376960358
NM_001202.3(BMP4):c.362A>G
TTCGTGGYGGAAGCTCCTCACGG
Microphthalmia syndromic 6



(p.His121Arg)







606231280
NM_001287223.1(SCN11A):c.1142T>C
CTTCAYTGTGGTCATTTTCCTGG,
Episodic pain syndrome, familial, 3



(p.Ile381Thr)
TTCAYTGTGGTCATTTTCCTGG





G






387906735
m.608A>G
TTCAGYGTATTGCTTTGAGGAGG






199474663
m.3260A>G
TTAAGTTYTATGCGATTACCGGG
Cardiomyopathy with or without





skeletal myopathy





104894962
NM_003413.3(ZIC3):c.1213A>G
TGTGTTYGCGCAGGGAGCTCGGG,
Heterotaxy, visceral, X-linked



(p.Lys405Glu)
ATGTGTTYGCGCAGGGAGCTCG





G






796053181
NM_021007.2(SCN2A):c.1271T>C
TGTGGYGGCCATGGCCTATGAGG
not provided



(p.Val424Ala)







267606788
NM_000129.3(F13A1):c.728T>C
TGTGAYGGACAGAGCACAAATGG
Factor xiii, a subunit, deficiency of



(p.Met243Thr)







397514503
NM_003863.3(DPM2):c.68A>G
TGTAGYAGGTGAAGATGATCAGG
Congenital disorder of glycosylation type



(p.Tyr23Cys)

1u





104893973
NM_000416.2(IFNGR1):c.260T>C
TGTAATAYTTCTGATCATGTTGG
Disseminated atypical mycobacterial



(p.Ile87Thr)

infection, Mycobacterium tuberculosis,





susceptibility to





121908466
NM_005682.6(ADGRG1):c.263A>G
TGGYAGAGGCCCCTGGGGTCAGG
Polymicrogyria, bilateral frontoparietal



(p.Tyr88Cys)







147952488
NM_002437.4(MPV17):c.186+2T>C
TGGYAAGTTCTCCCCTCAACAGG
Navajo neurohepatopathy





21909537
NM_001145.4(ANG):c.121A>G
TGGTTYGGCATCATAGTGCTGGG,
Amyotrophic lateral sclerosis type 9



(p.Lys41Glu)
GTGGTTYGGCATCATAGTGCTG





G






121918489
NM_000141.4(FGFR2):c.1018T>C
TGGGGAAYATACGTGCTTGGCGG,
Crouzon syndrome



(p.Tyr340His)
GGGGAAYATACGTGCTTGGCGGG






121434463
m.12320A>G
GAGTYGCACCAAAATTTTTGGGG,
Mitochondrial myopathy




GGAGTYGCACCAAAATTTTTGGG,





TGGAGTYGCACCAAAATTTTTG





G






121908046
NM_000403.3(GALE):c.101A>G
TGGAAGYTATCGATGACCACAGG
UDPglucose-4-epimerase deficiency



(p.Asn34Ser)







431905512
NM_003764.3(STX11):c.173T>C
TGCYGGTGGCCGACGTGAAGCGG
Hemophagocytic lymphohistiocytosis,



(p.Leu58Pro)

familial, 4





121917905
NM_000124.3(ERCC6):c.2960T>C
TGCYAAAAGACCCAAAACAAAGG
Cerebro-oculo-facio-skeletal syndrome



(p.Leu987Pro)







121918500
NM_000141.4(FGFR2):c.874A>G
TGCTYGATCCACTGGATGTGGGG,
Crouzon syndrome



(p.Lys292Glu)
GTGCTYGATCCACTGGATGTGGG,





CGTGCTYGATCCACTGGATGTG





G






60431989
NM_000053.3(ATP7B):c.3443T>C
TGCTGAYTGGAAACCGTGAGTGG
Wilson disease



(p.Ile1148Thr)







78950939
NM_000250.1(MPO):c.518A>G
GTGCGGYATTTGTCCTGCTCCGG,
Myeloperoxidase deficiency



(p.Tyr173Cys)
TGCGGYATTTGTCCTGCTCCGG





G






115677373
NM_201631.3(TGM5):c.763T>C
TGCGGAGYGGACGGGCAGCGTGG
Peeling skin syndrome, acral type



(p.Trp255Arg)







5030804
NM_000551.3(VHL):c.233A>G
GCGAYTGCAGAAGATGACCTGGG,
Von Hippel-Lindau syndrome



(p.Asn78Ser)
TGCGAYTGCAGAAGATGACCTG





G






397508328
NM_000492.3(CFTR):c.1A>G
GCAYGGTCTCTCGGGCGCTGGGG,
Cystic fibrosis



(p.Met1Val)
TGCAYGGTCTCTCGGGCGCTGGG,





CTGCAYGGTCTCTCGGGCGCTGG






137853299
NM_000362.4(TIMP3):c.572A>G
TGCAGYAGCCGCCCTTCTGCCGG
Sorsby fundus dystrophy



(p.Tyr191Cys)







121908549
NM_000334.4(SCN4A):c.3478A>G
TGAYGGAGGGGATGGCGCCTAGG




(p.Ile1160Val)







121909337
NM_001451.2(FOXF1):c.1138T>C
TGATGYGAGGCTGCCGCCGCAGG
Alveolar capillary dysplasia with



(p.Ter380Arg)

misalignment of pulmonary veins





281875320
NM_005359.5(SMAD4):c.1500A>G
TGAGYATGCATAAGCGACGAAGG
Myhre syndrome



(p.Ile500Met)







730880132
NM_170707.3(LMNA):c.710T>C
TGAGTYTGAGAGCCGGCTGGCGG
Primary dilated cardiomyopathy



(p.Phe237Ser)







281875322
NM_005359.5(SMAD4):c.1498A>G
TGAGTAYGCATAAGCGACGAAGG
Hereditary cancer-predisposing syndrome,



(p.Ile500Val)

Myhre syndrome





72556283
NM_000531.5(OTC):c.527A>G
TGAGGYAATCAGCCAGGATCTGG
not provided



(p.Tyr176Cys)







74315311
NM_020435.3(WC2):c.857T>C
TGAGAYGGCCCACCTGGGCTTGG,
Leukodystrophy, hypomyelinating, 2



(p.Met286Thr)
GAGAYGGCCCACCTGGGCTTGGG






121912495
NM_170707.3(LMNA):c.1139T>C
TCTYGGAGGGCGAGGAGGAGAGG
Congenital muscular dystrophy, LMNA-related



(p.Leu380Ser)







128620184
NM_000061.2(BTK):c.1288A>G
TCTYGATGGCCACGTCGTACTGG
X-linked agammaglobulinemia



(p.Lys430Glu)







118192252
NM_004519.3(KCNQ3):c.1403A>G
TCTTTAYTGTTTAAGCCAACAGG
Benign familial neonatal seizures 2, not



(p.Asn468Ser)

specified





121909142
NM_001300.5(KLF6):c.190T>C
TCTGYGGACCAAAATCATTCTGG




(p.Trp64Arg)







104895503
NM_001127255.1(NLRP7):c.2738A>G
TCTGGYTGATACTCAAGTCCAGG
Hydatidiform mole



(p.Asn913Ser)







587783035
NM_000038.5(APC):c 1744-2A>G
TCCYAGTAAGAAACAGAATATGG
Familial adenomatous polyposis





72556289
NM_000531.5(OTC):c.541-2A>G
TCCYAAAAGGCACGGGATGAAGG
not provided





28937313
NM_005502.3(ABCA1):c.2804A>G
TCCAYTGTGGCCCAGGAAGGAGG,
Tangier disease



(p.Asn935Ser)
CGCTCCAYTGTGGCCCAGGAAGG






143246552
NM_001003811.1(TEX11):c.511A>G
TCCAYGGTCAAGTCAGCCTCAGG,
Spermatogenic failure, X-linked, 2



(p.Met171Val)
CCAYGGTCAAGTCAGCCTCAGGG






587776451
NM_002049.3(GATA1):c.2T>C
CTCCAYGGAGTTCCCTGGCCTGG,
GATA-1-related thrombocytopenia



(p.Met1Thr)
TCCAYGGAGTTCCCTGGCCTGGG,
with dyserythropoiesis




CCAYGGAGTTCCCTGGCCTGGGG






121908403
NM_021102.3(SPINT2):c.488A>G
TCCAYAGATGAAGTTATTGCAGG
Diarrhea 3, secretory sodium, congenital,



(p.Tyr163Cys)

syndromic





281874738
NM_000495.4(COL4A5):c.438+2T>C
CTCCAGYAAGTTATAAAATTTGG,
Alport syndrome, X-linked recessive




TCCAGYAAGTTATAAAATTTGG





G






730880279
NM_030653.3(DDX11):c.2271+2T>C
TCCAGGYGCGGGCGTCATGCTGG,
Warsaw breakage syndrome




CCAGGYGCGGGCGTCATGCTGGG






28940272
NM_017890.4(VPS13B):c.8978A>G
TCAYTGATAAGCAGGGCCCAGGG,
Cohen syndrome, not specified



(p.Asn2993Ser)
TTCAYTGATAAGCAGGGCCCAGG






137852375
NM_000132.3(F8):c.5372T>C
TCAYGGTGAGTTAAGGACAGTGG
Hereditary factor VIII deficiency disease



(p.Met1791Thr)







11567847
NM_021961.5(TEAD1):c.1261T>C
TCATATTYACAGGCTTGTAAAGG




(p.Tyr?His)







786203989
NM_016069.9(PAM16):c.226A>G
CATAGTYCTGCAGAGGAGAGGGG,
Chondrodysplasia, megarbane-dagher-melki



(p.Asn76Asp)
TCATAGTYCTGCAGAGGAGAGGG
type





587776437
NC_012920.1:m.9478T>C
TCAGAAGYTTTTTTCTTCGCAGG
Leigh disease





121912474
NM_000424.3(KRT5):c.20T>C
TCAAGTGYGTCCTTCCGGAGCGG,
Epidermolysis bullosa simplex, Koebner type



(p.Val7Ala)
CAAGTGYGTCCTTCCGGAGCGGG,





AAGTGYGTCCTTCCGGAGCGGGG,





AGTGYGTCCTTCCGGAGCGGGGG






104886461
NM_020533.2(MCOLN1):c.406-2A>G
TACYGTGGGCAGAGAAGGGGAGG,
Ganglioside sialidase deficiency




AGGTACYGTGGGCAGAGAAGGGG,





CAGGTACYGTGGGCAGAGAAGGG






104894275
NM_000317.2(PTS):c.155A>G
TAAYTGTGCCCATGGCCATTTGG
6-pyruvoyl-tetrahydropterin synthase deficiency



(p.Asn52Ser)







587777562
NM_015599.2(PGM3):c.737A>G
TAAATGAYTGAGTTTGCCCTTGG
Immunodeficiency 23



(p.Asn246Ser)







121964906
NM_000027.3(AGA):c.916T>C
GTTATAYGTGCCAATGTGACTGG
Aspartylglycosaminuria



(p.Cys306Arg)







28941769
NM_000356.3(TCOF1):c.149A>G
GTGTGTAYAGATGTCCAGAAGGG
Treacher collins syndrome 1



(p.Tyr50Cys)







121434464
m.12297T>C
GTCYTAGGCCCCAAAAATTTTGG
Cardiomyopathy, mitochondrial





121908407
NM_054027.4(ANKH):c.143T>C
GTCGAGAYGCTGGCCAGCTACGG,
Chondrocalcinosis 2



(p.Met48Thr)
TCGAGAYGCTGGCCAGCTACGGG






59151893
NM_000422.2(KRT17):c.275A>G
GTCAYTGAGGTTCTGCATGGTGG,
Pachyonychia congenita type 2



(p.Asn92Ser)
GCGGTCAYTGAGGTTCTGCATGG






121909499
NM_002427.3(MMP13):c.272T>C
GTCAYGAAAAAGCCAAGATGCGG,




(p.Met91Thr)
TCAYGAAAAAGCCAAGATGCGG





G






61748478
NM_000552.3(VWF):c.2384A>G
GTCAYAGTTCTGGCACGTTTTGG
von Willebrand disease type 2N



(p.Tyr795Cys)







387906889
NM_006796.2(AFG3L2):c.1847A>G
GTAYAGAGGTATTGTTCTTTTGG
Spastic ataxia 5, autosomal recessive



(p.Tyr616Cys)







118203907
NM_000130.4(F5):c.5189A>G
GTAGYAGGCCCAAGCCCGACAGG
Factor V deficiency



(p.Tyr1730Cys)







118203945
NM_013319.2(UBIAD1):c.305A>G
GTAAGTGYTGACCAAATTACCGG
Schnyder crystalline corneal dystrophy



(p.Asn102Ser)







267607080
NM_005633.3(SOSI):c.1294T>C
GGTYGGGAGGGAAAAGACATTGG
Noonan syndrome 4, Rasopathy



(p.Trp432Arg)







137852953
NM_012464.4(TLL1):c.1885A>G
GGTTAYGGTGCCGTTAAGTTTGG
Atrial septal defect 6



(p.Ile629Val)







118203949
NM_013319.2(UBIAD1):c.695A>G
GGTGTTGYTGGAATGGAGAATGG
Schnyder crystalline corneal dystrophy



(p.Asn232Ser)







137852952
NM_012464.4(TLL1):c.713T>C
GGGATTGYTGTTCATGAATTGGG
Atrial septal defect 6



(p.Val238Ala)







41460449
m.3394T>C
GGCYATATACAACTACGCAAAGG
Leber optic atrophy





80357281
NM_007294.3(BRCA1):c.5291T>C
GGGCYAGAAATCTGTTGCTATGG,
Familial cancer of breast, Breast-ovarian



(p.Leu1764Pro)
GGCYAGAAATCTGTTGCTATGGG
cancer, familial 1





5030764
NM_000174.4(GP9):c.182A>G
GGCTGYTGTTGGCCAGCAGAAGG
Bernard-Soulier syndrome type C



(p.Asn61Ser)







72556282
NM_000531.5(OTC):c.526T>C
GGCTGATYACCTCACGCTCCAGG,
not provided



(p.Tyr176His)
GATYACCTCACGCTCCAGGTTGG






121913594
NM_000530.6(MPZ):c.242A>G
GGCATAGYGGAAGATCTATGAGG
Charcot-Marie-Tooth disease type 1B



(p.His8lArg)







587777736
NM_017617.3(NOTCH1):c.1285T>C
GGCAAGYGCATCAACACGCTGGG,
Adams-Oliver syndrome 1, Adams-



(p.Cys429Arg)
GGGCAAGYGCATCAACACGCTGG
Oliver syndrome 5





63750912
NM_016835.4(MAPT):c.1839T>C
GGATAAYATCAAACACGTCCCGG,
Frontotemporal dementia



(p.Asn613=)
GATAAYATCAAACACGTCCCGG





G






121918075
NM_000371.3(TTR):c.401A>G
GGAGYAGGGGCTCAGCAGGGCGG,
Amyloidogenic transthyretin amyloidosis



(p.Tyr134Cys)
ATAGGAGYAGGGGCTCAGCAGGG






730882063
NM_004523.3(KIF11):c.2547+2T>C
GGAGGYAATAACTTTGTAAGTGG
Microcephaly with or without





chorioretinopathy, lymphedema, or





mental retardation





397516156
NM_000257.3(MYH7):c.2546T>C
GGAGAYGGCCTCCATGAAGGAGG
Primary familial hypertrophic



(p.Met849Thr)

cardiomyopathy,





118204430
NM_000035.3(ALDOB):c.442T>C
GGAAGYGGCGTGCTGTGCTGAGG
Hereditary fructosuria



(p.Trp148Arg)







200198778
NM_013382.5(POMT2):c.1997A>G
GGAAGYAGTGGTGGAAGTAGAGG
Congenital muscular dystrophy, Congenital



(p.Tyr666Cys)

muscular dystrophy-dystroglycanopathy with





brain and eye anomalies, type A2, Muscular





dystrophy, Congenital muscular





dystrophy-dystroglycanopathy with mental retardation,





type B2





754896795
NM_004006.2(DMD):c.6982A>T
GCTTTTYTTCAAGCTGCCCAAGG
Duchenne muscular dystrophy, Becker



(p.Lys2328Ter)

muscular dystrophy, Dilated cardiomyopathy 3B





148924904
NM_000546.5(TP53):c.488A>G
GCTTGYAGATGGCCATGGCGCGG
Hereditary cancer-predisposing syndrome



(p.Tyr163Cys)







786204770
NM_016035.4(C0Q4):c.155T>C
GCTGTYGGCCGCCGGCTCCGCGG
COENZYME Q10 DEFICIENCY, PRIMARY, 7



(p.Leu52Ser)







121909520
NM_001100.3(ACTA1):c.350A>G
CGGYTGGCCTTGGGATTGAGGGG,
Nemaline myopathy 3



(p.Asn117Ser)
GCGGYTGGCCTTGGGATTGAGGG,





CGCGGYTGGCCTTGGGATTGAGG






587776879
NM_004656.3(BAP1):c.438-2A>G
GCCYGGGGAAAAACAGAGTCAGG
Tumor predisposition syndrome





727504434
NM_000501.3(ELN):c.890-2A>G
GCCYGAAAACACAGCCACAGAGG
Supravalvar aortic stenosis





119455953
NM_000391.3(TPP1):c.1093T>C
GCCGGGYGTTGGTCTGTCTCTGG
Ceroid lipofuscinosis, neuronal, 2



(p.Cys365Arg)







121964983
NM_000481.3(AMT):c.125A>G
GCCAGGYGGAAGTCATAGAGCGG
Non-ketotichyperglycinemia



(p.His42Arg)







121908300
NM_001005741.2(GBA):c.751T>C
GCCAGAYACTTTGTGAAGTAAGG,
Gaucher disease, type 1



(p.Tyr251His)
CCAGAYACTTTGTGAAGTAAGG






786205083
NM_003494.3(DYSF):c.3443-33A>G
GCCAGAGYGAGTGGCTGGAGTGG
Limb-girdle muscular dystrophy, type 2B





121908133
NM_175073.2(APTX):c.602A>G
GCCAAYGGTAACGGGCCTTTGGG,
Adult onset ataxia with oculomotor apraxia



(p.His201Arg)
AGCCAAYGGTAACGGGCCTTTGG






587777195
NM_005017.3(PCYT1A):c.571T>C
GCATGYTTGCTCCAACACAGAGG
Spondylometaphyseal dysplasia with cone-rod



(p.Phe191Leu)

dystrophy





431905520
NM_014714.3(IFT140):c.4078T>C
CAAGCAGYGTGAGCTGCTCCTGG,
Renal dysplasia, retinal pigmentary dystrophy,



(p.Cys1360Arg)
GCAGYGTGAGCTGCTCCTGGAGG
cerebellar ataxia and skeletal dysplasia





121912889
NM_001844.4(COL2A1):c.4172A>G
GCAGTGGYAGGTGATGTTCTGGG
Spondyloperipheral dysplasia, Platyspondylic



(p.Tyr1391Cys)

lethal skeletal dysplasia Torrance type





137854492
NM_001363.4(DKC1):c.1069A>G
GCAGGYAGAGATGACCGCTGTGG
Dyskeratosis congenita X-linked



(p.Thr357Ala)







121434362
NM_152783.4(D2HGDH):c.1315A>G
GCAGGTYACCATCTCCTGGAGGG,
D-2-hydroxyglutaric aciduria 1



(p.Asn439Asp)
TGCAGGTYACCATCTCCTGGAGG






80338732
NM_002764.3(PRPS1):c.344T>C
GCAAATAYGCTATCTGTAGCAGG
Charcot-Marie-Tooth disease, X-



(p.Met115Thr)

linked recessive, type 5





387906675
NM_000313.3(PROS1):c.701A>G
GATTAYATCTGTAGCCTTCGGGG,
Thrombophilia due to protein S deficiency,



(p.Tyr234Cys)
AGATTAYATCTGTAGCCTTCGGG,
autosomal recessive




GAGATTAYATCTGTAGCCTTCGG






28935478
NM_000061.2(BTK):c.1082A>G
GATGGYAGTTAATGAGCTCAGGG,




(p.Tyr36ICys)
TGATGGYAGTTAATGAGCTCAGG






201777056
NM_005050.3(ABCD4):c.956A>G
GATGAGGYAGATGCACACAAAGG
METHYLMALONIC ACIDURIA



(p.Tyr319Cys)

AND HOMOCYSTINURIA, cblJ





121918528
NM_000098.2(CPT2):c.359A>G
GATAGGYACATATCAAACCAGGG,
Carnitine palmitoyltransferase II



(p.TyrI20Cys)
AGATAGGYACATATCAAACCAG
deficiency, infantile




G






267607014
NM_002942.4(ROBO2):c.2834T>C
GAGAYTGGAAATTTTGGCCGTGG
Vesicoureteral reflux 2



(p.Ile945Thr)







281865192
NM_025114.3(CEP290):c.2991+1655
GATAYTCACAATTACAACTGGGG,
Leber congenital amaurosis 10



A>G
AGATAYTCACAATTACAACTGGG,





GAGATAYTCACAATTACAACTG






386833492
NM_000112.3(SLC26A2):c.-
GAGAGGYGAGAAGAGGGAAGCGG
Diastrophic dysplasia



26+2T>C







587779773
NM_001101.3(ACTB):c.356T>C
GAGAAGAYGACCCAGGTGAGTGG
Baraitser-Winter syndrome 1



(p.Met119Thr)







121913512
NM_000222.2(KIT):c.1924A>G
GACTTYGAGTTCAGACATGAGGG,




(p.Lys642Glu)
GGACTTYGAGTTCAGACATGAGG






28939072
NM_006329.3(FBLN5):c.506T>C
GACAYTGATGAATGTCGCTATGG
Age-related macular degeneration 3



(p.Ile169Thr)







104894248
NM_000525.3(KCNJ11):c.776A>G
GACAYGGTAGATGATCAGCGGGG,
Islet cell hyperplasia



(p.His259Arg)
TGACAYGGTAGATGATCAGCGGG,





ATGACAYGGTAGATGATCAGCGG






387907132
NM_016464.4(TMEM138):c.287A>G
GACAYGAAGGGAGATGCTGAGGG,
Joubert syndrome 16



(p.His96Arg)
AGACAYGAAGGGAGATGCTGAGG






121918170
NM_000275.2(OCA2):c.1465A>G
GACATYTGGAGGGTCCCCGATGG
Tyrosinase-positive oculocutaneous albinism



(p.Asn489Asp)







122467173
NM_014009.3(FOXP3):c.970T>C
GACAGAGYTCCTCCACAACATGG
Insulin-dependent diabetes mellitus secretory



(p.Phe324Leu)

diarrhea syndrome





137852268
NM_000133.3(F9):c.1328T>C
GAAYATATACCAAGGTATCCCGG
Hereditary factor LX deficiency disease



(p.Ile443Thr)







149054177
NM_001999.3(FBN2):c.3740T>C
GAATGTAYGATAATGAACGGAGG
not specified, Macular degeneration, early-



(p.Met1247Thr)

onset





137854488
NM_212482.1(FN1):c.2918A>G
GAAGTAAYAGGTGACCCCAGGGG
Glomerulopathy with fibronectin deposits 2



(p.Tyr973Cys)







786204027
NM_005957.4(MTHFR):c.1530+2T>C
GAAGGYGTGGTAGGGAGGCACGG,
Homocysteinemia due to MTHFR deficiency




AAGGYGTGGTAGGGAGGCACGGG,





AGGYGTGGTAGGGAGGCACGGGG






104894223
NM_012193.3(FZD4):c.766A>G
GAAATAYGATGGGGCGCTCAGGG,
Retinopathy of prematurity



(p.Ile256Val)
AGAAATAYGATGGGGCGCTCAGG






137854474
NM_000138.4(FBN1):c.3793T>C
CTTGYGTTATGATGGATTCATGG
Marfan syndrome



(p.Cys1265Arg)







587784418
NM_006306.3(SMC1A):c.3254A>G
CTTAYAGATCTCATCAATGTTGG
Congenital muscular hypertrophy-cerebral



(p.Tyr1085Cys)

syndrome





81002805
NM_000059.3(BRCA2):c.316+2T>C
CTTAGGYAAGTAATGCAATATGG
Familial cancer of breast, Breast-ovarian





cancer, familial 2, Hereditary cancer-predisposing syndrome





121909653
NM_182925.4(FLT4):c.3104A>G
CTGYGGATGCACTGGGGTGCGGG,




(p.His1035Arg)
TCTGYGGATGCACTGGGGTGCGG






786205107
NM_031226.2(CYP19A1):c.743+2T>C
CTGTGYAAGTAATACAACTTTGG
Aromatase deficiency





587777037
NM_001283009.1(RTEL1):c.3730T>C
CTGTGTGYGCCAGGGCTGTGGGG
Dyskeratosis congenita, autosomal recessive, 5



(p.Cys1244Arg)







794728380
NM_000238.3(KCNH2):c.1945+6T>C
CTGTGAGYGTGCCCAGGGGCGGG,
Cardiac arrhythmia




TGAGYGTGCCCAGGGGCGGGCGG






267607987
NM_000251.2(MSH2):c.2005+2T>C
CTGGYAAAAAACCTGGTTTTTGG,
Hereditary Nonpolyposis Colorectal Neoplasms




TGGYAAAAAACCTGGTTTTTGG





G






397509397
NM_006876.2(B4GAT1):c.1168A>G
TGATYTTCAGCCTCCTTTTGGGG,
Congenital muscular dystrophy-dystroglycanopathy



(p.Asn390Asp)
CTGATYTTCAGCCTCCTTTTGGG,
with brain and eye anomalies, type A13




GCTGATYTTCAGCCTCCTTTTGG






121918381
NM_000040.1(APOC3):c.280A>G
CTGAAGYTGGTCTGACCTCAGGG,




(p.Thr94Ala)
GCTGAAGYTGGTCTGACCTCAGG






104894919
NM_001015877.1(PHF6):c.769A>G
CTCYTGATGTTGTTGTGAGCTGG
Borjeson-Forssman-Lehmann syndrome



(p.Arg257Gly)







267606869
NM_005144.4(HR):c.-218A>G
CTCYAGGGCCGCAGGTTGGAGGG,
Marie Unna hereditary hypotrichosis 1




GCTCYAGGGCCGCAGGTTGGAGG,





GGCGCTCYAGGGCCGCAGGTTGG






139732572
NM_000146.3(FTL):c.1A>G
CTCAYGGTTGGTTGGCAAGAAGG
L-ferritin deficiency



(p.Met1Val)







397515418
NM_018486.2(HDAC8):c.1001A>G
CTCAYGATCTGGGATCTCAGAGG
Cornelia de Lange syndrome 5



(p.His334Arg)







372395294
NM_198056.2(SCN5A):c.1247A>G
CTCAYAGGCCATTGCGACCACGG
not provided



(p.Tyr416Cys)







104895304
NM_000431.3(MVK):c.803T>C
CTCAAYAGATGCCATCTCCCTGG
Hyperimmunoglobulin D with periodic



(p.Ile26811r)

fever, Mevalonic aciduria





587777188
NM_001165899.1(PDE4D):c.1850T>C
CTATAYTGTTCATCCCCTCTGGG,
Acrodysostosis 2, with or without hormone



(p.Ile617Thr)
ACTATAYTGTTCATCCCCTCTGG
resistance





398123026
NM_003867.3(FGF17):c.560A>G
CGTGGYTGGGGAAGGGCAGCTGG
Hypogonadotropic hypogonadism 20 with or



(p.Asn187Ser)

without anosmia





121964924
NM_001385.2(DPYS):c.1078T>C
CGTAATAYGGGAAAAAGGCGTGG,
Dihydropyrimidinase deficiency



(p.Trp360Arg)
AATAYGGGAAAAAGGCGTGGTGG,





ATAYGGGAAAAAGGCGTGGTGGG






587777301
NM_199189.2(MATR3):c.1864A>G
CGGYTGAACTCTCAGTCTTCTGG
Myopathy, distal, 2



(p.Thr622Ala)







200238879
NM_000527.4(LDLR):c.694+2T>C
ACTGCGGYATGGGCGGGGCCAGG,
Familial hypercholesterolemia




CTGCGGYATGGGCGGGGCCAGGG,





CGGYATGGGCGGGGCCAGGGTGG






142951029
NM_145046.4(CALR3):c.245A>G
CGGTYTGAAGCGTGCAGAGATGG
Arrhythmogenic right ventricular



(p.Lys82Arg)

cardiomyopathy, Familial





hypertrophic cardiomyopathy 19,





Hypertrophic cardiomyopathy





786200953
NM_006785.3(MALTI):c.1019-
CGCYTTGAAAAAAAAAGAAAGGG,
Combined immunodeficiency



2A>G
TCGCYTTGAAAAAAAAAGAAAG






120074192
NM_000218.2(KCNQ1):c.418A>G
CGCYGAAGATGAGGCAGACCAGG
Atrial fibrillation, familial, 3, Atrial fibrillation



(p.Ser140Gly)







267606887
NM_005957.4(MTHFR):c.971A>G
CGCGGYTGAGGGTGTAGAAGTGG
Homocystinuria due to MTHFR deficiency



(p.Asn324Ser)







118192117
NM_000540.2(RYR1):c.1205T>C
CGCAYGATCCACAGCACCAATGG
Congenital myopathy with fiber



(p.Met402Thr)

type disproportion, Central core





disease





199473625
NM_198056.2(SCN5A):c.4978A>G
CGAYGTTGAAGAGGGCAGGCAGG,
Brugada syndrome



(p.Ile1660Val)
AGCCCGAYGTTGAAGAGGGCAGG






794726865
NM_000921.4(PDE3A):c.1333A>G
CGAGGYGGTGGTGGTCCAAGTGG
Brachydactyly with hypertension



(p.Thr445Ala)







606231254
NM_005740.2(DNAL4):c.153+2T>C
CGAGGYATTGCCAGCAGTGCAGG
Mirror movements 3





786204826
NM_004771.3(MMP20):c.611A>G
CGAAAYGTGTATCTCCTCCCAGG
Amelogenesis imperfecta, hypomaturation type,



(p.His204Arg)

IIA2





796053139
NM_021007.2(SCN2A):c.4308+2T>C
CGAAATGYAAGTCTAGTTAGAGG,
not provided




GAAATGYAAGTCTAGTTAGAGG






137854494
NM_005502.3(ABCA1):c.4429T>C
CCTGTGYGTCCCCCAGGGGCAGG,
Tangier disease



(p.Cys1477Arg)
CTGTGYGTCCCCCAGGGGCAGGG,





TGTGYGTCCCCCAGGGGCAGGGG,





GTGYGTCCCCCAGGGGCAGGGGG






786205144
NM_001103.3(ACTN2):c.683T>C
CCTAAAAYGTTGGATGCTGAAGG
Dilated cardiomyopathy IAA



(p.Met228Thr)







199919568
NM_007254.3(PNKP):c.1029+2T>C
CCGGYGAGGCCCTGGGGCGGGGG,
not provided




TCCGGYGAGGCCCTGGGGCGGGG,





ATCCGGYGAGGCCCTGGGGCGGG,





GATCCGGYGAGGCCCTGGGGCGG






28939079
NM_018965.3(TREM2):c.401A>G
TGAYCCAGGGGGTCTATGGGAGG,
Polycystic lipomembranous osteodysplasia with



(p.Asp134Gly)
CGGTGAYCCAGGGGGTCTATGGG,
sclerosing leukoencephalopathy




CCGGTGAYCCAGGGGGTCTATGG






193302855
NM_032520.4(GNPTG):c.610-2A>G
CCCYGAAGGTGGAGGATGCAGGG,
Mucolipidosis III Gamma




GCCCYGAAGGTGGAGGATGCAGG






111033708
NM_000155.3(GALT):c.499T>C
CCCTYGGGTGCAGGTTTGTGAGG
Deficiency of UDPglucose-hexose-1-phosphate



(p.Trp167Arg)

uridylyltransferase





28933378
NM_000174.4(GP9):c.70T>C
CCCAYGTACCTGCCGCGCCCTGG
Bernard Soulier syndrome, Bernard-Soulier



(p.Cys24Arg)

syndrome type C





364897
NM_000157.3(GBA):c.680A>G
CCAYTGGTCTTGAGCCAAGTGGG,
Gaucher disease, Subacute neuronopathic



(p.Asn227Ser)
TCCAYTGGTCTTGAGCCAAGTGG
Gaucher disease, Gaucher disease, type 1





796052551
NM_000833.4(GRIN2A):c.2449A>G
CCAYGTTGTCAATGTCCAGCTGG
not provided



(p.Met817Val)







63751006
NM_002087.3(GRN):c.2T>C
CCAYGTGGACCCTGGTGAGCTGG
Frontotemporal dementia, ubiquitin-positive



(p.Met1Thr)







786203997
NM_001031.4(RPS28):c.1A>G
TGTCCAYGATGGCGGCGCGGCGG,
Diamond-Blackfan anemia with microtia and



(p.Met1Val)
CCAYGATGGCGGCGCGGCGGCGG
cleft palate





121908595
NM_002755.3(MAP2K1):c.389A>G
CCAYAGAAGCCCACGATGTACGG
Cardiofaciocutaneous syndrome 3, Rasopathy



(p.Tyr130Cys)







398122910
NM_000431.3(MVK):c.1039+2T>C
CCAGGYATCCCGGGGGTAGGTGG,
Porokeratosis, disseminated superficial actinic




CAGGYATCCCGGGGGTAGGTGGG
1





119474039
NM_020365.4(EIF2B3):c.1037T>C
CCAGAYTGTCAGCAAACACCTGG
Leukoencephalopathy with vanishing white



(p.Ile346Thr)

matter





587777866
NM_000076.2(CDKN1C):c.*5+2T>C
CCAAGYGAGTACAGCGCACCTGG,
Beckwith-Wiedemann syndrome




CAAGYGAGTACAGCGCACCTGGG,





AAGYGAGTACAGCGCACCTGGGG






121918530
NM_005587.2(MEF2A):c.788A>G
AGAYTACCACCACCTGGTGGAGG,




(p.Asn263Ser)
CCAAGAYTACCACCACCTGGTGG






483352818
NM_000211.4(ITGB2):c.1877+2T>C
CATGYGAGTGCAGGCGGAGCAGG
Leukocyte adhesion deficiency type 1





460184
NM_000186.3(CFH):c.3590T>C
CAGYTGAATTTGTGTGTAAACGG
Atypical hemolytic-uremic syndrome 1



(p.Val1197Ala)







121908423
NM_004795.3(KL):c.578A>G
CAGYGGTACAGGGTGACCACGGG,




(p.His193Arg)
CCAGYGGTACAGGGTGACCACGG






281860300
NM_005247.2(FGF3):c.146A>G
CAGYAGAGCTTGCGGCGCCGGGG,
Deafness with labyrinthine aplasia microtia and



(p.Tyr49Cys)
GCAGYAGAGCTTGCGGCGCCGGG,
microdontia (LAIVIM)




CGCAGYAGAGCTTGCGGCGCCGG






28935488
NM_000169.2(GLA):c.806T>C
CAGTTAGYGATTGGCAACTTTGG
Fabry disease



(p.Val269Ala)







587776514
NM_173560.3(RFX6):c.380+2T>C
CAGTGGYGAGACTCGCCCGCAGG,
Mitchell-Riley syndrome




AGTGGYGAGACTCGCCCGCAGGG






104894117
NM_178138.4(LHX3):c.332A>G
CAGGTGGYACACGAAGTCCTGGG
Pituitary hormone deficiency, combined 3



(p.Tyr111Cys)







34878913
NM_000184.2(HBG2):c.125T>C
CAGAGGTYCTTTGACAGCTTTGG
Cyanosis, transient neonatal



(p.Phe42Ser)







120074124
NM_000543.4(SMPD1):c.911T>C
AGCACYTGTGAGGAAGTTCCTGG,
Sphingomyelin/cholesterol lipidosis,Niemann-



(p.Leu304Pro)
GCACYTGTGAGGAAGTTCCTGGG,
Pick disease, type A, Niemann-Pick disease,




CACYTGTGAGGAAGTTCCTGGGG
type B





281860272
NM_005211.3(CSF1R):c.2320-2A>G
CACYGAGGGAAAGCACTGCAGGG,
Hereditary diffuse leukoencephalopathy with




GCACYGAGGGAAAGCACTGCAGG
spheroids





128624216
NM_000033.3(ABCD1):c.443A>G
CACTGYTGACGAAGGTAGCAGGG,
Adrenoleukodystrophy



(p.Asn148Ser)
GCACTGYTGACGAAGGTAGCAGG






398124257
NM_012463.3(ATP6V0A2):c.825+2
CACTGYGAGTAAGCTGGAAGTGG
Cutis laxa with osteodystrophy



T>C







267606679
NM_004183.3(BEST I):c.704T>C
CACTGGYGTATACACAGGTGAGG
Vitreoretinochoroidopathy dominant



(p.Val235Ala)







397514518
NM_000344.3(SMNI):c.388T>C
CACTGGAYATGGAAATAGAGAGG
Kugelberg-Welander disease



(p.Tyr130His)







143946794
NM_001946.3(DUSP6):c.566A>G
CACTAYTGGGGTCTCGGTCAAGG
Hypogonadotropic hypogonadism 19 with or



(p.Asn189Ser)

without anosmia





397516076
NM_000256.3(MYBPC3):c.821+
GCACGYGAGTGGCCATCCTCAGG,
Familial hypertrophic cardiomyopathy 4, not



2T
>CCACGYGAGTGGCCATCCTCAGGG
specified





149977726
NM_001257988.1(TYMP):c.665A>G
CACGAGTYTCTTACTGAGAATGG,




(p.Lys222Arg)
GAGTYTCTTACTGAGAATGGAGG






121917770
NM_003361.3(UMOD):c.383A>G
CACAYTGACACATGTGGCCAGGG,
Familial juvenile gout



(p.Asn128Ser)
CCACAYTGACACATGTGGCCAGG






121909008
NM_000492.3(CFTR):c.2738A>G
CACATAAYACGAACTGGTGCTGG
Cystic fibrosis



(p.Tyr913Cys)







137852819
NM_003688.3(CASK):c.2740T>C
CACAGYGGGTCCCTGTCTCCTGG,
FG syndrome 4



(p.Trp914Arg)
ACAGYGGGTCCCTGTCTCCTGGG






74315320
NM_024009.2(GM3):c.421A>G
CAAYGATGAGCTTGAAGATGAGG
Deafness, autosomal recessive



(p.Ile141Val)







80356747
NM_001701.3(BAAT):c.967A>G
CAAYGAAGAGGAATTGCCCCTGG
Atypical hemolytic-uremic syndrome 1



(p.Ile323Val)







180177324
NM_012203.1(GRHPR):c.934A>G
CAAGTYGTTAGCTGCCAACAAGG
Primary hyperoxaluria, type II



(p.Asn312Asp)







281860274
NM 005211.3(CSFIR):c.238IT>C
CAAGAYTGGGGACTTCGGGCTGG
Hereditary diffuse leukoencephalopathy with



(p.Ile794Thr)

spheroids





398122908
NM_005334.2(HCFC1):c.-
CAAGAYGGCGGCTCCCAGGGAGG
Mental retardation 3, X-linked



970T>C







548076633
NM_002693.2(POLG):c.3470A>G
CAAGAGGYTGGTGATCTGCAAGG
not provided



(p.Asn1157Ser)







120074146
NM_000019.3(ACAT1):c.935T>C
CAAGAAYAGTAGGTAAGGCCAGG
Deficiency of acetyl-CoA acetyltransferase



(p.Ile312Thr)







397514489
NM_005340.6(HINT1):c.250T>C
CAAGAAAYGTGCTGCTGATCTGG,
Gamstorp-Wohlfart syndrome



(p.Cys84Arg)
AAGAAAYGTGCTGCTGATCTGGG






587783539
NM_178151.2(DCX):c.2T>C
CAAAATAYGGAACTTGATTTTGG
Heterotopia



(p.Met1Thr)







104894765
NM_005448.2(BMP15):c.704A>G
ATTGAAAYAGAGTAACAAGAAGG
Ovarian dysgenesis 2



(p.Tyr235Cys)







137852429
NM_000132.3(F8):c.1892A>G
ATGYTGGAGGCTTGGAACTCTGG
Hereditary factor VIII deficiency disease



(p.Asn631Ser)







72558441
NM_000531.5(OTC):c.779T>C
ATGTATYAATTACAGACACTTGG
not provided



(p.Leu260Ser)







398123765
NM_003494.3(DYSF):c.1284+2T>C
ATGGYAAGGAGCAAGGGAGCAGG
Limb-girdle muscular dystrophy, type 2B





387906924
NM_020191.2(MRPS22):c.644T>C
ATCYTAGGGTAAGGTGACTTAGG
Combined oxidative phosphorylation deficiency



(p.Leu215Pro)

5





397518039
NM_206933.2(USH2A):c.8559-
ATCYAAAGCAAAAGACAAGCAGG
Retinitis pigmentosa, Usher syndrome, type 2A



2A>G







5742905
NM_000071.2(CBS):c.833T>C
ATCAYTGGGGTGGATCCCGAAGG,
Homocystinuria due to CBS



(p.Ile278Thr)
TCAYTGGGGTGGATCCCGAAGGG
deficiency, Homocystinuria,





pyridoxine-responsive





397507473
NM_004333.4(BRAF):c.403T>C
ATCATYTGGAACAGTCTACAAGG,
Cardiofaciocutaneous syndrome, Rasopathy



(p.Phe468Ser)
TCATYTGGAACAGTCTACAAGG






786204056
NM_000264.3(PTCHH:c.3168+2T>C
ATCATTGYGAGTGTATTATAAGG,
Gorlin syndrome




TCATTGYGAGTGTATTATAAGGG,





CATTGYGAGTGTATTATAAGGG






72558484
NM_000531.5(OTC):c.1005+2T>C
ATCATGGYAAGCAAGAAACAAGG
not provided





199473074
NM_000335.4(SCN5A):c.688A>G
ATAYAGTTTTCAGGGCCCGGAGG,
Brugada syndrome



(p.Ile230Val)
CTGATAYAGTTTTCAGGGCCCGG






111033273
NM_206933.2(USH2A):c.1606T>C
ATATAGAYGCCTCTGCTCCCAGG
Usher syndrome, type 2A



(p.Cys536Arg)







72556290
NM_000531.5(OTC):c.542A>G
ATAGTGTYCCTAAAAGGCACGGG
not provided



(p.Glu181Gly)







121918711
NM_004612.3(TGFBR1):c.1199A>G
ATAGATGYCAGCACGTTTGAAGG
Loeys-Dietz syndrome 1



(p.Asp400Gly)







104886288
NM_000495.4(COL4A5):c.4699T>C
AGTAYGTGAAGCTCCAGCTGTGG
Alport syndrome, X-linked recessive



(p.Cys1567Arg)







144637717
NM_016725.2(FOLRH:c.493+2T>C
CTTCAGGYGAGGGCTGGGGTGGG,
not provided




AGGYGAGGGCTGGGGTGGGCAGG






72558492
NM_000531.5(OTC):c.1034A>G
AGGTGAGYAATCTGTCAGCAGGG
not provided



(p.Tyr345Cys)







62638745
NM_000121.3(EPOR):c.1460A>G
AGGGYTGGAGTAGGGGCCATCGG
Acute myeloid leukemia, M6 type,



(p.Asn487Ser)

Familial erythrocytosis, 1





387907021
NM_031427.3(DNAL1):c.449A>G
AGGGAYTGCCTACAAACACCAGG
Kartagener syndrome, Ciliary dyskinesia,



(p.Asn150Ser)

primary, 16





397514488
NM_001161581.1(POC1A):c.398T>C
AGCYGTGGGACAAGAGCAGCCGG
Short stature, onychodysplasia, facial



(p.Leu133Pro)

dysmorphism, and hypotrichosis





154774633
NM_017882.2(CLN6):c.200T>C
AGCYGGTATTCCCTCTCGAGTGG
Adult neuronal ceroid lipofuscinosis



(p.Leu67Pro)







111033700
NM_000155.3(GALT):c.482T>C
AGCYGGGTGCCCAGTACCCTTGG
Deficiency of UDPglucose-hexose-1-phosphate



(p.Leu161Pro)

uridylyltransferase





128621198
NM_000061.2(BTK):c.1223T>C
GAGCYGGGGACTGGACAATTTGG,
X-linked agammaglobulinemia



(p.Leu408Pro)
AGCYGGGGACTGGACAATTTGGG






137852611
NM_000211.4(ITGB2):c.446T>C
AGCYAGGTGGCGACCTGCTCCGG
Leukocyte adhesion deficiency



(p.Leu149Pro)







121908838
NM_003722.4(TP63):c.697A>G
AGCTTYTTTGTAGACAGGCATGG
Split-hand/foot malformation 4



(p.Lys233Glu)







397515869
NM_000169.2(GLA):c.1153A>G
AGCTGTGYGATGAAGCAGGCAGG
not specified



(p.Thr385Ala)







118204064
NM_000237.2(LPL):c.548A>G
GCTGGAYCGAGGCCTTAAAAGGG,
Hyperlipoproteinemia, type I



(p.Asp183Gly)
AGCTGGAYCGAGGCCTTAAAAGG






128620186
NM_000061.2(BTK):c.2T>C
AGCTAYGGCCGCAGTGATTCTGG
X-linked agammaglobulinemia



(p.Met1Thr)







786204132
NM_014946.3(SPAST):c.1165A>G
ATTGYCTTCCCATTCCCAGGTGG,
Spastic paraplegia 4, autosomal dominant



(p.Thr389Ala)
AGCATTGYCTTCCCATTCCCAGG






199473661
NM_000218.2(KCNQ1):c.550T>C
CAGCAAGBACGTGGGCCTCTGGG,
Congenital long QT syndrome, Cardiac



(p.Tyr184His)
AGCAAGBACGTGGGCCTCTGGGG,
arrhythmia




GCAAGBACGTGGGCCTCTGGGGG






387907129
NM_024599.5(RHBDF2):c.557T>C
AGAYTGTGGATCCGCTGGCCCGG
Howel-Evans syndrome



(p.Ile186Thr)







387906702
NM_006306.3(SMC1A):c.2351T>C
AGAYTGGTGTGCGCAACATCCGG
Congenital muscular hypertrophy-cerebral



(p.Ile784Thr)

syndrome





193929348
NM_000525.3(KCNJ11):c.544A>G
AGAYGAGGGTCTCAGCCCTGCGG
Permanent neonatal diabetes mellitus



(p.Ile182Val)







121908934
NM_004086.2(COCH):c.1535T>C
AGATAYGGCTTCTAAACCGAAGG
Deafness, autosomal dominant 9



(p.Met512Thr)







397514377
NM_000060.3(BTD):c.641A>G
AGAGGYTGTGTTTACGGTAGCGG
Biotinidase deficiency



(p.Asn214Ser)







72552295
NM_000531.5(OTC):c.2T>C
AGAAGAYGCTGTTTAATCTGAGG
not provided



(p.Met1Thr)







201893545
NM_016247.3(IMPG2):c.370T>C
ACTYTTTGGGATCGACTTCCTGG
Macular dystrophy, vitelliform, 5



(p.Phe124Leu)







121434469
m.4290T>C
ACTYTGATAGAGTAAATAATAGG






121918733
NM_006920.4(SCN1A):c.269T>C
ACTTYTATAGTATTGAATAAAGG,
Severe myoclonic epilepsy in infancy



(p.Phe90Ser)
CTTYTATAGTATTGAATAAAGG





G






121434471
m.4291T>C
ACTTYGATAGAGTAAATAATAGG
Hypertension, hypercholesterolemia, and





hypomagnesemia, mitochondrial





606231289
NM_001302946.1(TRNT1):c.497T>C
ACTTYATTTGACTACTTTAATGG
Sideroblastic anemia with B-cell



(p.Leu166Ser)

immunodeficiency, periodic fevers,





and developmental delay





63750067
NM_000517.4(HBA2):c.*92A>G
CTTYATTCAAAGACCAGGAAGGG,
Hemoglobin H disease, nondeletional




ACTTYATTCAAAGACCAGGAAG





G






121918734
NM_006920.4(SCN1A):c.272T>C
ACTTTTAYAGTATTGAATAAAGG,
Severe myoclonic epilepsy in infancy



(p.Ile91Thr)
CTTTTAYAGTATTGAATAAAGG





G






137854557
NM_000267.3(NF1):c.1466A>G
ACTTAYAGCTTCTTGTCTCCAGG
Neurofibromatosis, type 1



(p.Tyr489Cys)







397514626
NM_018344.5(SLC29A3):c.607T>C
ACTGATAYCAGGTGAGAGCCAGG,
Histiocytosis-lymphadenopathy plus syndrome



(p.Ser203Pro)
CTGATAYCAGGTGAGAGCCAGGG






118204440
NM_000512.4(GALNS):c.1460A>G
ACGYTGAGCTGGGGCTGCGCGGG,
Mucopolysaccharidosis, MPS-IV-A



(p.Asn487Ser)
CACGYTGAGCTGGGGCTGCGCGG






587776843
NG_012088.1:g.2209A>G
ACCYTATGATCCGCCCGCCTTGG






137853033
NM_001080463.1(DYNC2H1):c.4610A>G
ACCYGTGAAGGGAACAGAGATGG
Short-rib thoracic dysplasia 3 with or



(p.Gln1537Arg)

without polydactyly





28933698
NM_000435.2(NOTCH3):c.1363T>C
TTCACCYGTATCTGTATGGCAGG,
Cerebral autosomal dominant arteriopathy with



(p.Cys455Arg)
ACCYGTATCTGTATGGCAGGTGG
subcortical infarcts and leukoencephalopathy




ACCYGAGATGCAAAATAGGGAGG,






587776766
NM_000463.2(UGT1A1):c.1085-2A>G
GTGACCYGAGATGCAAAATAGGG,
Crigler Najjar syndrome, type 1




GGTGACCYGAGATGCAAAATAGG






587781628
NM_001128425.1(MUTYH):c.1187-2A>G
ACCYGAGAGGGAGGGCAGCCAGG
Hereditary cancer-predisposing syndrome,





Carcinoma of colon





61755817
NM_000322.4(PRPH2):c.736T>C
ACCTGYGGGTGCGTGGCTGCAGG,
Retinitis pigmentosa



(p.Trp246Arg)
CCTGYGGGTGCGTGGCTGCAGGG






121909184
NM_001089.2(ABCA3):c.1702A>G
ACCGTYGTGGCCCAGCAGGACGG
Surfactant metabolism dysfunction, pulmonary,



(p.Asn568Asp)

3





121434466
m.4269A>G
ACAYATTTCTTAGGTTTGAGGGG,





GACAYATTTCTTAGGTTTGAGGG,





AGACAYATTTCTTAGGTTTGAGG






794726768
NM_001165963.1(SCN1A):c.1048A>G
ACAYATATCCCTCTGGACATTGG
Severe myoclonic epilepsy in infancy



(p.Met350Val)







28934876
NM_001382.3(DPAGT1):c.509A>G
ACAYAGTACAGGATTCCTGCGGG,
Congenital disorder of glycosylation type 1J



(p.Tyr170Cys)
GACAYAGTACAGGATTCCTGCGG






104894749
NM_000054.4(AVPR2):c.614A>G
ACAYAGGTGCGACGGCCCCAGGG,
Nephrogenic diabetes insipidus, Nephrogenic



(p.Tyr205Cys)
GACAYAGGTGCGACGGCCCCAGG
diabetes insipidus, X-linked





128621205
NM_000061.2(BTK):c.1741T>C
ACATTYGGGCTTTTGGTAAGTGG
X-linked agammaglobulinemia



(p.Trp581Arg)







28940892
NM_000529.2(MC2R):c.761A>G
ACATGYAGCAGGCGCAGTAGGGG,
ACTH resistance



(p.Tyr254Cys)
GACATGYAGCAGGCGCAGTAGGG,





AGACATGYAGCAGGCGCAGTAGG






794726844
NM_001165963.1(SCN1A):c.1046A>G
ACATAYATCCCTCTGGACATTGG
Severe myoclonic epilepsy in infancy



(p.Tyr349Cys)







587783083
NM_003159.2(CDKL5):c.449A>G
ACAGTYTTAGGACATCATTGTGG
not provided



(p.Lys150Arg)







397514651
NM_000108.4(DLD):c.140T>C
ACAGTTAYAGGTTCTGGTCCTGG,
Maple syrup urine disease, type 3



(p.Ile47Thr)
GTTAYAGGTTCTGGTCCTGGAGG






794727060
NM_001848.2(COL6A1):c.957+2T>C
ACAAGGYGAGCGTGGGCTGCTGG,
Ullrich congenital muscular dystrophy, Bethlem




CAAGGYGAGCGTGGGCTGCTGGG
myopathy





72554346
NM_000531.5(OTC):c.284T>C
ACAAGATYGTCTACAGAAACAGG
not provided



(p.Leu95Ser)







483353031
NM_002136.2(HNRNPA1):c.841T>C
AATYTTGGAGGCAGAAGCTCTGG
Chronic progressive multiple sclerosis



(p.Phe281Leu)







104894271
NM_000315.2(PTH):c.52T>C
AATTYGTTTTCTTACAAAATCGG
Hypoparathyroidism familial isolated



(p.Cys18Arg)







267608260
NM_015599.2(PGM3):c.248T>C
AATGTYGGCACCATCCTGGGAGG
Immunodeficiency 23



(p.Leu83Ser)







267606900
NM_018109.3(MTPAP):c.1432A>G
AATGGATYCTGAATGTACAGAGG
Ataxia, spastic, 4, autosomal recessive



(p.Asn478Asp)







796053169
NM_021007.2(SCN2A):c.387-
AATAAAGYAGAATATCGTCAAGG
not provided



2A>G







104894937
NM_000116.4(TAZ):c.352T>C
AAGYGTGTGCCTGTGTGCCGAGG
3-Methylglutaconic aciduria type 2



(p.Cys118Arg)







104893911
NM_001018077.1(NR3C1):c.1712T>C
AAGYGATTGCAGCAGTGAAATGG
Pseudohermaphroditism, female, with



(p.Val571Ala)

hypokalemia, due to glucocorticoid resistance





397514472
NM_004813.2(PEX16):c.992A>G
AAGYAGATTTTCTGCCAGGTGGG,
Peroxisome biogenesis disorder 8B



(p.Tyr331Cys)
GAAGYAGATTTTCTGCCAGGTGG,





GTAGAAGYAGATTTTCTGCCAGG






121918407
NM_001083112.2(GPD2):c.1904T>C
AAGTYTGATGCAGACCAGAAAGG
Diabetes mellitus type 2



(p.Phe635Ser)







63751110
NM_000251.2(MSH2):c.595T>C
AAGGAAYGTGTTTTACCCGGAGG
Hereditary Nonpolyposis Colorectal Neoplasms



(p.Cys199Arg)







119450945
NM_000026.2(ADSL):c.674T>C
AAGAYGGTGACAGAAAAGGCAGG
Adenylosuccinate lyase deficiency



(p.Met225Thr)







113993988
NM_002863.4(PYGL):c.2461T>C
AAGAAYATGCCCAAAACATCTGG
Glycogen storage disease, type VI



(p.Tyr821His)







119485091
NM_022041.3(GAN):c.1268T>C
AAGAAAAYCTACGCCATGGGTGG,
Giant axonal neuropathy



(p.Ile423Thr)
AAAAYCTACGCCATGGGTGGAGG






137852419
NM_000132.3(F8):c.1660A>G
AACYAGAGTAATAGCGGGTCAGG
Hereditary factor VIII deficiency disease



(p.Ser554Gly)







121964967
NM_000071.2(CBS):c.1150A>G
AACTYGGTCCTGCGGGATGGGGG,
Homocystinuria,pyridox ne-respons ve



(p.Lys384Glu)
GAACTYGGTCCTGCGGGATGGGG,





GGAACTYGGTCCTGCGGGATGGG,





AGGAACTYGGTCCTGCGGGATGG






137852376
NM_000132.3(F8):c.1754T>C
AACAGAYAATGTCAGACAAGAGG
Hereditary factor VIII deficiency disease



(p.Ile585Thr)







121917930
NM_006920.4(SCN1A):c.3577T>C
AACAAYGGTGGAACCTGAGAAGG
Generalized epilepsy with febrile seizures plus,



(p.Trp1193Arg)

type 1, Generalized epilepsy with febrile





seizures plus, type 2





28939717
NM_003907.2(EIF2B5):c.271A>G
AAATGYTTCCTGTACACCTGTGG
Leukoencephalopathy with vanishing white



(p.Thr91Ala)

matter





80357276
NM_007294.3(BRCA1):c.122A>G
AAATATGYGGTCACACTTTGTGG
Familial cancer of breast, Breast-ovarian



(p.His41Arg)

cancer, familial 1





397515897
NM_000256.3(MYBPC3):c.1351+2T>C
AAAGGYGGGCCTGGGACCTGAGG
Familial hypertrophic cardiomyopathy





4, Cardiomyopathy





397514491
NM_005340.6(HINT I):c.152A>G
AAAAYGTGTTGGTGCTTGAGGGG,
Gamstorp-Wohlfart syndrome



(p.His5lArg)
GAAAAYGTGTTGGTGCTTGAGGG,





AGAAAAYGTGTTGGTGCTTGAGG






387907164
NM_020894.2(UVSSA):c.94T>C
AAAATTYGCAAGTATGTCTTAGG,
UV-sensitive syndrome 3



(p.Cys32Arg)
AAATTYGCAAGTATGTCTTAGG





G






118161496
NM_025152.2(NUBPL):c.815-
TGGTTCYAATGGATGTCTGCTGG,
Mitochondrial complex I deficiency



27T>C
GGTTCYAATGGATGTCTGCTGGG






764313717
NM_005609.2(PYGM):c.425_528del
TGGCTGYCAGGGACCCAGCAAGG,





CTGYCAGGGACCCAGCAAGGAGG






28934568
NM_003242.5(TGFBR2):c.923T>C
AGTTCCYGACGGCTGAGGAGCGG
Loeys-Dietz syndrome 2



(p.Leu308Pro)







121913461
NM_007313.2(ABL1):c.814T>C
CCAGYACGGGGAGGTGTACGAGG,




(p.Tyr272His)
CAGYACGGGGAGGTGTACGAGGG






377750405
NM_173551.4(ANKS6):c.1322A>G
AGGGCYGTCGGACCTTCGAGTGG,
Nephronophthisis 16



(p.Gln441Arg)
GGGCYGTCGGACCTTCGAGTGGG,





GGCYGTCGGACCTTCGAGTGGGG






57639980
NM_001927.3(DES):c.1034T>C
ATTCCCYGATGAGGCAGATGCGG,
Myofibrillar myopathy 1



(p.Leu345Pro)
TTCCCYGATGAGGCAGATGCGGG






147391618
NM_020320.3(RARS2):c.35A>G
ATACCYGGCAAGCAATAGCGCGG
Pontocerebellar hypoplasia type 6



(p.Gln12Arg)







182650126
NM_002977.3(SCN9A):c.2215A>G
GTAAYTGCAAGATCTACAAAAGG
Small fiber neuropathy



(p.Ile739Val)







80358278
NM_004700.3(KCNQ4):c.842T>C
ACATYGACAACCATCGGCTATGG
DFNA 2 Nonsyndromic Hearing Loss



(p.Leu281Ser)







786204012
NM_005957.4(MTHFR):c.388T>C
GACCYGCTGCCGTCAGCGCCTGG
Homocysteinemia due to MTHFR deficiency



(p.Cys130Arg)







786204037
NM_005957.4(MTHFR):c.1883T>C
TCCCACYGGACAACTGCCTCTGG
Homocysteinemia due to MTHFR deficiency



(p.Leu628Pro)







202147607
NM_000140.3(FECH):c.1137+3A>G
GTAGAYACCTTAGAGAACAATGG
Erythropoieticprotoporphyria





122456136
NM_005183.3(CACNA1F):c.2267T>C
TGCCAYTGCTGTGGACAACCTGG




(p.Ile756Thr)







786204851
NM_007374.2(SIX6):c.110T>C
GTCGCYGCCCGTGGCCCCTGCGG
Cataract, microphthalmia and nystagmus



(p.Leu37Pro)







794728167
NM_000138.4(FBN1):c.1468+2T>C
ATTGGYACGTGATCCATCCTAGG
Thoracic aortic aneurysms and aortic





dissections





121964909
NM_000027.3(AGA):c.214T>C
GACGGCYCTGTAGGCTTTGGAGG
Aspartylglycosaminuria



(p.Ser72Pro)







121964978
NM_000170.2(GLDC):c.2T>C
CGGCCAYGCAGTCCTGTGCCAGG,
Non-ketotichyperglycinemia



(p.Met1Thr)
GGCCAYGCAGTCCTGTGCCAGGG






121965008
NM_000398.6(CYB5R3):c.446T>C
CTGCYGGTCTACCAGGGCAAAGG
METHEMOGLOBINEMIA, TYPE I



(p.Leu149Pro)







121965064
NM_000128.3(F1 1 ):c.90IT>C
TGATYTCTTGGGAGAAGAACTGG
Hereditary factor XI deficiency disease



(p.Phe301Leu)







45517398
NM_000548.3(TSC2):c.5150T>C
GCCCYGCACGCAAATGTGAGTGG,
Tuberous sclerosis syndrome



(p.Leu1717Pro)
CCCYGCACGCAAATGTGAGTGGG






786205857
NM_015662.2(IFT172):c.770T>C
TTGTGCYAGGAAGTTATGACAGG
RETINITIS PIGMENTOSA 71



(p.Leu257Pro)







786205904
NM_001135669.1(XPR1):c.653T>C
GCGTTYACGTGTCCCCCCTTTGG,
BASAL GANGLIA



(p.Leu218Ser)
CGTTYACGTGTCCCCCCTTTGGG
CALCIFICATION,





104893704
NM_000388.3(CASR):c.2641T>C
ACGCTYTCAAGGTGGCTGCCCGG,
Hypercalciuric hypercalcemia



(p.Phe881Leu)
CGCTYTCAAGGTGGCTGCCCGGG






104893747
NM_I98159.2(MITF):c.1195T>C
ACTTYCCCTTATTCCATCCACGG,
Waardenburg syndrome type 2A



(p.Ser399Pro)
CTTYCCCTTATTCCATCCACGGG






104893770
NM_000539.3(RHO):c.133T>C
CATGYTTCTGCTGATCGTGCTGG,
Retinitis pigmentosa 4



(p.Phe45Leu)
ATGYTTCTGCTGATCGTGCTGGG






28937596
NM_003907.2(EIF2B5):c.1882T>C
AGGCCYGGAGCCCTGTTTTTAGG
Leukoencephalopathy with vanishing white



(p.Trp628Arg)

matter





104893876
NM_001151.3(SLC25A4):c.293T>C
GCAGCYCTTCTTAGGGGGTGTGG
Autosomal dominant progressive external



(p.Leu98Pro)

ophthalmoplegia with mitochondrial





DNA deletions 2





104893883
NM_006005.3(WFS1):c.2486T>C
ACCATCCYGGAGGGCCGCCTGGG
WFS1-Related Disorders



(p.Leu829Pro)







104893962
NM_000165.4(GJA1):c.52T>C
CTACYCAACTGCTGGAGGGAAGG
Oculodentodigital dysplasia



(p.Ser18Pro)










104893978
NM_000434.3(NEU1):c.718T>C
GCCTCCYGGCGCTACGGAAGTGG,
Sialidosis, type II



(p.Trp240Arg)
CCTCCYGGCGCTACGGAAGTGGG,





CTCCYGGCGCTACGGAAGTGGGG






104894092
NM_002546.3(TNFRSF11B):c.349T>C
TAGAGYTCTGCTTGAAACATAGG
Hyperphosphatasemia with bone disease



(p.Phe117Leu)







104894135
NM_000102.3(CYP17A1):c.316T>C
CATCGCGYCCAACAACCGTAAGG,
Complete combined 17-alpha-



(p.Ser106Pro)
ATCGCGYCCAACAACCGTAAGGG
hydroxylase/17,20-lyase





104894151
NM_000102.3(CYP17A1):c.1358T>C
AGCTCTYCCTCATCATGGCCTGG
Combined partial 17-alpha-hydroxylase/17,20-



(p.Phe453Ser)

lyase deficiency





36015961
NM_000518.4(HBB):c.344T>C
TGTGTGCYGGCCCATCACTTTGG
Beta thalassemia intermedia



(p.Leu115Pro)







104894472
NM_152443.2(RDH12):c.523T>C
TCCYCGGTGGCTCACCACATTGG
Leber congenital amaurosis 13



(p.Ser175Pro)







104894587
NM_004870.3(MPDU1):c.356T>C
TTCCYGGTCATGCACTACAGAGG
Congenital disorder of glycosylation type 1F



(p.Leu119Pro)







104894588
NM_004870.3(MPDUI):c.2T>C
AATAYGGCGGCCGAGGCGGACGG
Congenital disorder of glycosylation type 1F



(p.Met1Thr)







104894626
NM_000304.3(PMP22):c.82T>C
TAGCAAYGGATCGTGGGCAATGG
Charcot-Marie-Tooth disease, type IE



(p.Trp28Arg)







104894631
NM_018129.3(PNP0):c.784T>C
ACCTYAACTCTGGGACCTGCTGG
“Pyridoxal 5-phosphate-dependent epilepsy”



(p.Ter262Gln)







104894703
NM_032551.4(KISS1R):c.305T>C
GCCCTGCYGTACCCGCTGCCCGG,




(p.Leu102Pro)
TGCYGTACCCGCTGCCCGGCTGG






104894826
NM_000166.5(GJBI):c.407T>C
ATGYCATCAGCGTGGTGTTCCGG
Dejerine-Sottas disease, X-linked hereditary



(p.Val136Ala)

motor and sensory neuropathy





104894859
NM_001122606.1(LAIVIP2):c.961T>C
CAGCTACYGGGATGCCCCCCTGG,
Danon disease



(p.Trp321Arg)
AGCTACYGGGATGCCCCCCTGGG






104894931
NM_006517.4(SLC16A2):c.1313T>C
TGAGCYGGTGGGCCCAATGCAGG
Allan-Herndon-Dudley syndrome



(p.Leu438Pro)







104894935
NM_000330.3(RS1):c.38T>C
TTACTTCYCTTTGGCTATGAAGG
Juvenile retinoschisis



(p.Leu13Pro)







104895217
NM_001065.3(TNFRSF1A):c.175T>C
TGCYGTACCAAGTGCCACAAAGG
TNF receptor-associated periodic fever



(p.Cys59Arg)

syndrome (TRAPS)





143889283
NM_003793.3(CTSF):c.692A>G
CTCCAYACTGAGCTGTGCCACGG
Ceroid lipofuscinosis, neuronal, 13



(p.Tyr231Cys)







122459147
NM_001159702.2(FHL1):c.310T>C
GGGGYGCTTCAAGGCCATTGTGG
Myopathy, reducing body, X-linked,



(p.Cys104Arg)

childhood- onset





74552543
NM_020184.3(CNNM4):c.971T>C
AAGCTCCYGGACTTTTTTCTGGG
Cone-rod dystrophy amelogenesis imperfecta



(p.Leu324Pro)







199476117
m.10158T>C
AAAYCCACCCCTTACGAGTGCGG
Leigh disease, Leigh syndrome due to





mitochondrial complex I deficiency,





Mitochondrial complex I deficiency





794727808
NM_020451.2(SEPN1):c.872+2T>C
TTCCGGYGAGTGGGCCACACTGG
Congenital myopathy with fiber type





disproportion, Eichsfeld type





congenital muscular dystrophy





140547520
NM_005022.3(PFN1):c.350A>G
CACCTYCTTTGCCCATCAGCAGG
Amyotrophic lateral sclerosis 18



(p.Glu117Gly)







397514359
NM_000060.3(BTD):c.445T>C
TCACCGCYTCAATGACACAGAGG
Biotinidase deficiency



(p.Phe149Leu)







207460001
m.15197T>C
CTAYCCGCCATCCCATACATTGG
Exercise intolerance





397514406
NM_000060.3(BTD):c.1214T>C
TTCACCCYGGTCCCTGTCTGGGG
Biotinidase deficiency



(p.Leu405Pro)







397514516
NM_006177.3(NRL):c.287T>C
GAGGCCAYGGAGCTGCTGCAGGG
Retinitis pigmentosa 27



(p.Met96Thr)







72554312
NM_000531.5(OTC):c.134T>C
CTCACTCYAAAAAACTTTACCGG
Ornithine carbamoyltransferase deficiency



(p.Leu45Pro)







397514569
NM_178012.4(TUBB2B):c.350T>C
GGTCCYGGATGTGGTGAGGAAGG
Polymicrogyria, asymmetric



(p.Leu117Pro)







397514571
NM_000431.3(MVK):c.122T>C
CGGCYTCAACCCCACAGCAATGG,
Porokeratosis, disseminated superficial actinic



(p.Leu41Pro)
GGCYTCAACCCCACAGCAATGGG
1





794728390
NM_000238.3(KCNH2):c.2396T>C
GCCATCCYGGGTATGGGGTGGGG,
Cardiac arrhythmia



(p.Leu799Pro)
CCATCCYGGGTATGGGGTGGGGG,





CATCCYGGGTATGGGGTGGGGGG






397514713
NM_001199107.1(TBC1D24):c.686T>C
GGTCTYTGACGTCTTCCTGGTGG
Early infantile epileptic encephalopathy 16



(p.Phe229Ser)







397514719
NM_080605.3(B3GALT6):c.193A>G
CGCYGGCCACCAGCACTGCCAGG
Spondyloepimetaphyseal dysplasia with joint



(p.Ser65Gly)

laxity





730880608
NM_000256.3(MYBPC3):c.3796T>C
GAGYGCCGCCTGGAGGTGCGAGG
Cardiomyopathy



(p.Cys1266Arg)







397515329
NM_001382.3(DPAGTH:c.503T>C
AATCCYGTACTATGTCTACATGG,
Congenital disorder of glycosylation type 1J



(p.Leu168Pro)
ATCCYGTACTATGTCTACATGGG,





TCCYGTACTATGTCTACATGGGG






397515465
NM_018127.6(ELAC2):c.460T>C
ATAYTTTCTGGTCCATTGAAAGG
Combined oxidative phosphorylation deficiency



(p.Phe154Leu)

17





397515557
NM_005211.3(CSF1R):c.2483T>C
CATCTYTGACTGTGTCTACACGG
Hereditary diffuse leukoencephalopathy with



(p.Phe828Ser)

spheroids





397515599
NM_194248.2(0T0F):c.3413T>C
AGGTGCYGTTCTGGGGCCTACGG,
Deafness, autosomal recessive 9



(p.Leu1138Pro)
GGTGCYGTTCTGGGGCCTACGGG






397515766
NM_000138.4(FBN1):c.2341T>C
GGACAAYGTAGAAATACTCCTGG
Marfan syndrome



(p.Cys781Arg)







565779970
NM_001429.3(EP300):c.3573T>A
CTTAYTACAGTTACCAGAACAGG
Rubinstein-Taybi syndrome 2



(p.Tyr1191Ter)







786200938
NM_080605.3(B3GALT6):c.1A>G
AGCTTCAYGGCGCCCGCGCCGGG,
Spondyloepimetaphyseal dysplasia with joint



(p.Met1Val)
TCAYGGCGCCCGCGCCGGGCCGG
laxity





28942087
NM_000229.1(LCAT):c.698T>C
ATCTCTCYTGGGGCTCCCTGGGG,
Norum disease



(p.Leu233Pro)
TCTCYTGGGGCTCCCTGGGGTGG






128621203
NM_000061.2(BTK):c.1625T>C
TCGGCCYGTCCAGGTGAGTGTGG
X-linked agammaglobulinemia with



(p.Leu542Pro)

growth hormone deficiency





397515412
NM_006383.3(CIB2):c.368T>C
CTTCAYCTGCAAGGAGGACCTGG
Deafness, autosomal recessive 48



(p.Ile123Thr)







193929364
NM_000352.4(ABCC8):c.404T>C
AAGCYGCTAATTGGTAGGTGAGG
Permanent neonatal diabetes mellitus



(p.Leu135Pro)







730880872
NM_000257.3(MYH7):c.1400T>C
TCGAGAYCTTCGATGTGAGTTGG,
Cardiomyopathy



(p.Ile467Thr)
CGAGAYCTTCGATGTGAGTTGGG






80356474
NM_002977.3(SCN9A):c.2543T>C
AAGATCAYTGGTAACTCAGTAGG,
Primary erythromelalgia



(p.Ile848Thr)
AGATCAYTGGTAACTCAGTAGGG,





GATCAYTGGTAACTCAGTAGGGG






80356489
NM_001164277.1(SLC37A4):c.352T>C
GGGCYGGCCCCCATGTGGGAAGG
Glucose-6-phosphate transport defect



(p.Trp118Arg)







80356536
NM_152296.4(ATP1A3):c.2338T>C
GCCCYTCCTGCTGTTCATCATGG
Dystonia 12



(p.Phe780Leu)







80356596
NM_194248.2(0T0F):c.3032T>C
GATGCYGGTGTTCGACAACCTGG
Deafness, autosomal recessive 9, Auditory



(p.Leu1011Pro)

neuropathy, autosomal recessive, 1





80356689
NM_000083.2(CLCN1):c.857T>C
AGGAGYGCTATTTAGCATCGAGG
Myotonia congenita



(p.Val286Ala)







118203884
m.4409T>C
AGGYCAGCTAAATAAGCTATCGG
Mitochondrial myopathy





587777625
NM_173596.2(SLC39A5):c.911T>C
AGAACAYGCTGGGGCTTTTGCGG
Myopia 24, autosomal dominant



(p.Met304Thr)







587783087
NM_003159.2(CDKL5):c.602T>C
ATTCYTGGGGAGCTTAGCGATGG
not provided



(p.Leu201Pro)







118203951
NM_013319.2(UBIAD1):c.511T>C
TCTGGCYCCTTTCTCTACACAGG,
Schnyder crystalline corneal dystrophy



(p.Ser171Pro)
GGCYCCTTTCTCTACACAGGAGG






118204017
NM_000018.3(ACADVL):c.1372T>C
TCGCATCYTCCGGATCTTTGAGG,
Very long chain acyl-CoA dehydrogenase



(p.Phe458Leu)
CGCATCYTCCGGATCTTTGAGGG,
deficiency




GCATCYTCCGGATCTTTGAGGGG






397518466
NM_000833.4(GRIN2A):c.2T>C
CTAYGGGCAGAGTGGGCTATTGG
Focal epilepsy with speech disorder with or



(p.Met1Thr)

without mental retardation





118204069
NM_000237.2(LPL):c.337T>C
GGACYGGCTGTCACGGGCTCAGG
Hyperlipoproteinemia, type I



(p.Trp113Arg)







118204080
NM_000237.2(LPL):c.755T>C
GTGAYTGCAGAGAGAGGACTTGG
Hyperlipoproteinemia, type I



(p.Ile252Thr)







118204111
NM_000190.3(HMBS):c.739T>C
GCTTCGCYGCATCGCTGAAAGGG
Acute intermittent porphyria



(p.Cys247Arg)







80357438
NM_007294.3(BRCA1):c.65T>C
AAATCTYAGAGTGTCCCATCTGG
Familial cancer of breast, Breast-ovarian



(p.Leu22Ser)

cancer, familial 1, Hereditary cancer-predisposing syndrome





139877390
NM_001040431.2(COA3):c.215A>G
CCAYCTGGGGAGGTAGGTTCAGG




(p.Tyr72Cys)







793888527
NM_005859.4(PURA):c.563T>C
GACCAYTGCGCTGCCCGCGCAGG,
not provided, Mental retardation, autosomal



(p.Ile188Th)
ACCAYTGCGCTGCCCGCGCAGGG,
dominant 31




CCAYTGCGCTGCCCGCGCAGGGG






561425038
NM_002878.3(RAD51D):c.1A>G
CGCCCAYGTTCCCCGCAGGCCGG
Hereditary cancer-predisposing syndrome



(p.Met1Val)







121907934
NM_024105.3(ALG12):c.473T>C
TCCYGCTGGCCCTCGCGGCCTGG
Congenital disorder of glycosylation type 1G



(p.Leu158Pro)







80358207
NM_153212.2(GM4):c.409T>C
CCTCATCYTCAAGGCCGCCGTGG
Erythrokeratodermia variabilis



(p.Phe137Leu)







80358228
NM_002353.2(TACSTD2):c.557T>C
TCGGCYGCACCCCAAGTTCGTGG
Lattice conical dystrophy Type III



(p.Leu186Pro)







121908076
NM_138691.2(TMC1):c.1543T>C
AGGACCTYGCTGGGAAACAATGG,
Deafness, autosomal recessive 7



(p.Cys515Arg)
ACCTYGCTGGGAAACAATGGTGG,





CCTYGCTGGGAAACAATGGTGGG






121908089
NM_017838.3(NHP2):c.415T>C
GGAGGCTYACGATGAGTGCCTGG,
Dyskeratosis congenita autosomal recessive 1,



(p.Tyr139His)
GGCTYACGATGAGTGCCTGGAGG
Dyskeratosis congenita, autosomal recessive 2





121908154
NM_001243133.1(NLRP3):c.926T>C
GGTGCCTYTGACGAGCACATAGG
Familial cold urticaria, Chronic infantile



(p.Phe309Ser)

neurological, cutaneous and articular syndrome





121908158
NM_001033855.2(DCLRE1C):c.2T>C
GGCGCTAYGAGTTCTTTCGAGGG,
Histiocytic medullary reticulosis



(p.Met1Thr)
GCGCTAYGAGTTCTTTCGAGGGG






796052870
NM_018129.3(PNP0):c.2T>C
CCCCCAYGACGTGCTGGCTGCGG,
not provided



(p.Met1Thr)
CCCCAYGACGTGCTGGCTGCGGG,





CCCAYGACGTGCTGGCTGCGGGG






121908318
NM_020427.2(SLURP1):c.43T>C
GCAGCCYGGAGCATGGGCTGTGG
Acroerythrokeratoderma



(p.Trpl5Arg)







121908352
NM_022124.5(CDH23):c.5663T>C
CTCACCTYCAACATCACTGCGGG
Deafness, autosomal recessive 12



(p.Phe1888Ser)







121908520
NM_000030.2(AGXT):c.613T>C
CCTGTACYCGGGCTCCCAGAAGG
Primary hyperoxaluria, type I



(p.Ser205Pro)







121908618
NM_004273.4(CHST3):c.920T>C
CGTGCYGGCCTCGCGCATGGTGG
Spondyloepiphyseal dysplasia with congenital



(p.Leu307Pro)

joint dislocations





11694
NM_006432.3(NPC2):c.199T>C
TATTCAGYCTAAAAGCAGCAAGG
Niemann-Pick disease type C2



(p.Ser67Pro)







121908739
NM_000022.2(ADA):c.320T>C
CCTGCYGGCCAACTCCAAAGTGG
Severe combined immunodeficiency due to



(p.Leu107Pro)

ADA deficiency





80359022
NM_000059.3(BRCA2):c.7958T>C
TGCYTCTTCAACTAAAATACAGG
Familial cancer of breast, Breast-ovarian



(p.Leu2653Pro)

cancer, familial 2





121908902
NM_003880.3(WISP3):c.232T>C
AAAATCYGTGCCAAGCAACCAGG,
Progressive pseudorheumatoid dysplasia



(p.Cys78Arg)
AAATCYGTGCCAAGCAACCAGGG,





AATCYGTGCCAAGCAACCAGGGG






121908947
NM_006892.3(DNMT3B):c.808T>C
CAAGTTCYCCGAGGTGAGTCCGG,
Centromeric instability of chromosomes 1,9 and



(p.Ser270Pro)
AAGTTCYCCGAGGTGAGTCCGGG,
16 and immunodeficiency




AGTTCYCCGAGGTGAGTCCGGGG






121909028
NM_000492.3(CFTR):c.3857T>C
AGCCTYTGGAGTGATACCACAGG
Cystic fibrosis



(p.Phe1286Ser)







121909135
NM_000085.4(CLCNKB):c.1294T>C
CTTTGTCYATGGTGAGTCTGGGG
Bartter syndrome type 3



(p.Tyr432His)







121909143
NM_001300.5(KLF6):c.506T>C
GGAGCYGCCCTCGCCAGGGAAGG




(p.Leu169Pro)







121909182
NM_001089.2(ABCA3):c.302T>C
GCACYTGTGATCAACATGCGAGG
Surfactant metabolism dysfunction, pulmonary,



(p.Leu101Pro)

3





121909200
NM_000503.5(EYA1):c.1459T>C
CACTCYCGCTCATTCACTCCCGG
Melnick-Fraser syndrome



(p.Ser487Pro)







121909247
NM_004970.2(IGFALS):c.1618T>C
GGACYGTGGCTGCCCTCTCAAGG
Acid-labile subunit deficiency



(p.Cys540Arg)







121909253
NM_005570.3(LMAN1):c.2T>C
AGAYGGCGGGATCCAGGCAAAGG
Combined deficiency of factor V and factor



(p.Met1Thr)

VIII, 1





121909385
NM_000339.2(SLC12A3):c.1868T>C
CAACCYGGCCCTCAGCTACTCGG
Familial hypokalemia-hypomagnesemia



(p.Leu623Pro)







121909497
NM_002427.3(MMP13):c.224T>C
TTCTYCGGCTTAGAGGTGACTGG
Spondyloepimetaphyseal dysplasia, Missouri



(p.Phe75Ser)

type





121909508
NM_000751.2(CHRND):c.188T>C
AACCYCATCTCCCTGGTGAGAGG
MYASTHENIC SYNDROME,



(p.Leu63Pro)

CONGENITAL, 3B, FAST-





CHANNEL





121909519
NM_001100.3(ACTA1):c.287T>C
CGAGCYTCGCGTGGCTCCCGAGG
Nemaline myopathy 3



(p.Leu96Pro)







121909572
NM_000488.3(SERPINC1):c.667T>C
TGGGTGYCCAATAAGACCGAAGG
Antithrombin III deficiency



(p.Ser223Pro)







121909677
NM_000821.6(GGCX):c.896T>C
TATGTYCTCCTACGTCATGCTGG
Pseudoxanthoma elasticum-like disorder with



(p.Phe299Ser)

multiple coagulation factor deficiency





121909727
NM_001018077.1(NR3C1):c.2209T>C
CTATTGCYTCCAAACATTTTTGG
Glucocorticoid resistance, generalized



(p.Phe737Leu)







139573311
NM_000492.3(CFTR):c.1400T>C
TTCACYTCTAATGGTGATTATGG,
Cystic fibrosis



(p.Leu467Pro)
TCACYTCTAATGGTGATTATGGG






121912441
NM_000454.4(SOD1):c.341T>C
CATCAYTGGCCGCACACTGGTGG
Amyotrophic lateral sclerosis type 1



(p.Ile114Thr)







121912446
NM_000454.4(SOD1):c.434T>C
CGTTYGGCTTGTGGTGTAATTGG,
Amyotrophic lateral sclerosis type 1



(p.Leu145Ser)
GTTYGGCTTGTGGTGTAATTGGG






121912463
NM_000213.3(ITGB4):c.1684T>C
GGCCAGYGTGTGTGTGAGCCTGG
Epidermolysis bullosa with pyloric atresia



(p.Cys562Arg)







121912492
NM_002292.3(LAIVIB2):c.961T>C
CCTCAACYGCGAGCAGTGTCAGG
Nephrotic syndrome, type 5, with or



(p.Cys321Arg)

without ocular abnormalities





397516659
NM_001399.4(EDA):c.2T>C
GGCCAYGGGCTACCCGGAGGTGG
Hypohidrotic X-linked ectodermal dysplasia



(p.Met1Thr)







111033589
NM_021044.2(DHH):c.485T>C
GTTGCYGGCGCGCCTCGCAGTGG
46, XY gonadal dysgenesis, complete, dhh-



(p.Leu162Pro)

related





111033622
NM_000206.2(IL2RG):c.343T>C
TGGCYGTCAGTTGCAAAAAAAGG
X-linked severe combined immunodeficiency



(p.Cys115Arg)







121912613
NM_001041.3(SI):c.1859T>C
ATGCYGGAGTTCAGTTTGTTTGG
Sucrase-isomaltase deficiency



(p.Leu620Pro)







121912619
NM_016180.4(SLC45A2):c.1082T>C
GAGTTTCYCATCTACGAAAGAGG
Oculocutaneous albinism type 4



(p.Leu361Pro)







61750581
NM_000552.3(VWF):c.4837T>C
CTGCCYCTGATGAGATCAAGAGG
von Willebrand disease, type 2a



(p.Ser1613Pro)







121912653
NM_000546.5(TP53):c.755T>C
CATCCYCACCATCATCACACTGG
Li-Fraumeni syndrome 1



(p.Leu252Pro)







111033683
NM_000155.3(GALT):c.386T>C
AGGTCAYGTGCTTCCACCCCTGG
Deficiency of UDPglucose-hexose-1-phosphate



(p.Met129Thr)

uridylyltransferase





111033752
NM_000155.3(GALT):c.677T>C
CAGGAGCYACTCAGGAAGGTGGG
Deficiency of UDPglucose-hexose-1-phosphate



(p.Leu226Pro)

uridylyltransferase





121912729
NM_000039.1(AP0A1):c.593T>C
GCGCTYGGCCGCGCGCCTTGAGG
Familial visceral amyloidosis, Ostertag type



(p.Leu198Ser)







769452
NM_000041.3(APOE):c.137T>C
AACYGGCACTGGGTCGCTTTTGG




(p.Leu46Pro)







121912762
NM_016124.4(RHD):c.329T>C
ACACYGTTCAGGTATTGGGATGG




(p.Leu110Pro)







111033824
NM_000155.3(GALT):c.1138T>C
CGCCYGACCACGCCGACCACAGG,
Deficiency of UDPglucose-hexose-1-phosphate



(p.Ter380Arg)
GCCYGACCACGCCGACCACAGGG
uridylyltransferase





111033832
NM_000155.3(GALT):c.980T>C
TCCYGCGCTCTGCCACTGTCCGG
Deficiency of UDPglucose-hexose-1-phosphate



(p.Leu327Pro)

uridylyltransferase





730881974
NM_000455.4(STK11):c.545T>C
GGGAACCYGCTGCTCACCACCGG,
Hereditary cancer-predisposing syndrome



(p.Leu182Pro)
AACCYGCTGCTCACCACCGGTGG






1064644
NM_000157.3(GBA):c.703T>C
GGGYCACTCAAGGGACAGCCCGG
Gaucher disease



(p.Ser235Pro)







796052090
NM_138413.3(HOGA1):c.533T>C
GGACCYGCCTGTGGATGCAGTGG
Primary hyperoxaluria, type III



(p.Leu178Pro)







121913141
NM_000208.2(INSR):c.779T>C
CTACCYGGACGGCAGGTGTGTGG
Leprechaunism syndrome



(p.Leu260Pro)







121913272
NM_006218.2(PIK3CA):c.1258T>C
GGAACACYGTCCATTGGCATGGG,
Congenital lipomatous overgrowth, vascular



(p.Cys420Arg)
GAACACYGTCCATTGGCATGGGG
malformations, and epidermal nevi, Neoplasm





of ovary, PIK3CA Related Overgrowth





Spectrum





61751310
NM_000552.3(VWF):c.8317T>C
GCTCCYGCTGCTCTCCGACACGG
von Willebrand disease, type 2a



(p.Cys2773Arg)







312262799
NM_024408.3(NOTCH2):c.1438T>C
TTCACAYGTCTGTGCATGCCAGG
Alagille syndrome 2



(p.Cys480Arg)







121913570
NM_000426.3(LAIVIA2):c.7691T>C
ATCATTCYTTTGGGAAGTGGAGG,
Merosin deficient congenital



(p.Leu2564Pro)
TCATTCYTTTGGGAAGTGGAGGG
muscular dystrophy





121913640
NM_000257.3(MYH7):c.1046T>C
AACTCCAYGTATAAGCTGACAGG
Familial hypertrophic cardiomyopathy



(p.Met349Thr)

1, Cardiomyopathy





121913642
NM_000257.3(MYH7):c.1594T>C
CATCATGYCCATCCTGGAAGAGG
Dilated cardiomyopathy 1S



(p.Ser532Pro)







119463996
NM_001079802.1(FKTN):c.527T>C
GTAGTCTYTCATGAGAGGAGTGG
Limb-girdle muscular



(p.Phe176Ser)

dystrophy-





587776456
NM_002049.3(GATA1):c.1240T>C
GCTCAYGAGGGCACAGAGCATGG
GATA-1-related thrombocytopenia



(p.Ter414Arg)

with dyserythropoiesis





63750654
NM_000184.2(HBG2):c.-228T>C
ATGCAAAYATCTGTCTGAAACGG
Fetal hemoglobin quantitative trait locus 1





587776519
NM_001999.3(FBN2):c.3725-15A>G
AGCAYTGCAACCACATTGTCAGG
Congenital contractural arachnodactyly





78365220
NM_000402.4(G6PD):c.473T>C
TGCCCYCCACCTGGGGTCACAGG
Anemia, nonspherocytic hemolytic, due to



(p.Leu158Pro)

G6PD deficiency





63750741
NM_000179.2(MSH6):c.1346T>C
CTGGGGCYGGTATTCATGAAAGG
Hereditary Nonpolyposis Colorectal Neoplasms



(p.Leu449Pro)







587776914
NM_017565.3(FAIVI20A):c.590-2A>G
GTAATCYGCAAAGGAGGAGAAGG,
Enamel-renal syndrome




TAATCYGCAAAGGAGGAGAAGG






5030809
NM_000551.3(VHL):c.292T>C
CCCYACCCAACGCTGCCGCCTGG
Von Hippel-Lindau syndrome,



(p.Tyr98His)

Hereditary cancer-predisposing





syndrome





199476132
m.5728T>C
CAATCYACTTCTCCCGCCGCCGG,
Cytochrome-c oxidase deficiency, Mitochondrial




AATCYACTTCTCCCGCCGCCGGG
complex I deficiency





62637012
NM_014336.4(AIPL1):c.715T>C
CTGCCAGYGCCTGCTGAAGAAGG,
Leber congenital amaurosis 4



(p.Cys239Arg)
CCAGYGCCTGCTGAAGAAGGAGG






199476199
NM_207352.3(CYP4V2):c.1021T>C
AAACTGGYCCTTATACCTGTTGG,
Bietti crystalline comeoretinal dystrophy



(p.Ser341Pro)
AACTGGYCCTTATACCTGTTGGG






587777183
NM_006702.4(PNPLA6):c.3053T>C
CCTYTAACCGCAGCATCCATCGG
Boucher Neuhauser syndrome



(p.Phe1018Ser)







199476389
NM_000487.5(ARSA):c.899T>C
GGTCTCTYGCGGTGTGGAAAGGG
Metachromatic leukodystrophy



(p.Leu300Ser)







199476398
NM_016599.4(MYOZ2):c.142T>C
TTAYCCCATCTCAGTAACCGTGG
Familial hypertrophic cardiomyopathy 16



(p.Ser48Pro)







119456967
NM_001037633.1(SIL1):c.1370T>C
TTGCYGAAGGAGCTGAGATGAGG
Marinesco-Sj\xc3\xb6gren syndrome



(p.Leu457Pro)







730882253
NM_006888.4(CALM1):c.268T>C
GGCAYTCCGAGTCTTTGACAAGG
Long QT syndrome 14



(p.Phe90Leu)







587777283
NM_012338.3(TSPAN12):c.413A>G
TAATCCAYAATTTGTCATCCTGG
Exudative vitreoretinopathy 5



(p.Tyr138Cys)







587777306
NM_015884.3(MBTPS2):c.1391T>C
GCTYTGCTTTGGATGGACAATGG
Palmoplantar keratoderma, mutilating, with



(p.Phe464Ser)

periorificial keratotic plaques, X-linked





56378716
NM_000250.1(MPO):c.752T>C
TCACTCAYGTTCATGCAATGGGG
Myeloperoxidase deficiency



(p.Met251Thr)







587777390
NM_005026.3(PIK3CD):c.1246T>C
GCAGGACYGCCCCATTGCCTGGG
Activated PI3K-delta syndrome



(p.Cys416Arg)







587777480
NM_003108.3(SOXI 1 ):c.I78T>C
TATGGYCCAAGATCGAACGCAGG
Mental retardation, autosomal dominant 27



(p.Ser60Pro)







587777663
NM_001288767.1(ARMC5):c.1379T>C
GCCCGACYGCGGGATGCTGGTGG
Acth-independent macronodular adrenal



(p.Leu460Pro)

hyperplasia 2





61753033
NM_000350.2(ABCA4):c.5819T>C
AAGGCYACATGAACTAACCAAGG
Stargardt disease, Stargardt disease 1, Cone-rod dystrophy 3



(p.Leu1940Pro)







200488568
NM_002972.3(SBF1):c.4768A>G
CAGGCGYCCTCTTGCTCAGCCGG
Charcot-Marie-Tooth disease, type 4B3



(p.Thr1590Ala)







132630274
NM_000377.2(WAS):c.809T>C
CGGAGTCYGTTCTCCAGGGCAGG
Severe congenital neutropenia X-linked



(p.Leu270Pro)







132630308
NM_001399.4(EDA):c.181T>C
CTGCYACCTAGAGTTGCGCTCGG
Hypohidrotic X-linked ectodermal dysplasia



(p.Tyr61His)







60934003
NM_170707.3(LMNA):c.1589T>C
ACGGCTCYCATCAACTCCACTGG,
Benign scapuloperoneal muscular dystrophy



(p.Leu530Pro)
CGGCTCYCATCAACTCCACTGGG,
with cardiomyopathy




GGCTCYCATCAACTCCACTGGGG






180177160
NM_000030.2(AGXT):c.1076T>C
GGTGCYGCGGATCGGCCTGCTGG,
Primary hyperoxaluria, type I



(p.Leu359Pro)
GTGCYGCGGATCGGCCTGCTGGG






180177222
NM_000030.2(AGXT):c.449T>C
GTGCYGCTGTTCTTAACCCACGG,
Primary hyperoxaluria, type I



(p.Leu150Pro)
TGCYGCTGTTCTTAACCCACGGG






180177254
NM_000030.2(AGXT):c.661T>C
GCTCATCYCCTTCAGTGACAAGG
Primary hyperoxaluria, type I



(p.Ser221Pro)







180177264
NM_000030.2(AGXT):c.757T>C
GGGGCYGTGACGACCAGCCCAGG
Primary hyperoxaluria, type I



(p.Cys253Arg)







180177293
NM_000030.2(AGXT):c.893T>C
GTATCYGCATGGGCGCCTGCAGG
Primary hyperoxaluria, type I



(p.Leu298Pro)







376785840
NM_001282227.1(CECR1):c.1232A>G
GAAATCAYAGGACAAGCCTTTGG
Polyarteritis nodosa



(p.Tyr411Cys)







587779393
NM_000257.3(MYH7):c.4937T>C
GAGCCYCCAGAGCTTGTTGAAGG
Myopathy, distal, 1



(p.Leu1646Pro)







587779410
NM_012434.4(SLC17A5):c.500T>C
ATTGTACYCAGAGCACTAGAAGG
Sialic acid storage disease, severe infantile



(p.Leu167Pro)

type





587779513
NM_000090.3(COL3A1):c.2337+2T>C
AGGYAACCCTTAATACTACCTGG
Ehlers-Danlos syndrome, type 4



(p.Gly762_Lys779del)







777539013
NM_020376.3(PNPLA2):c.757+2T>C
GAACGGYGCGCGGACCCGGGCGG,
Neutral lipid storage disease with myopathy




AACGGYGCGCGGACCCGGGCGGG






34557412
NM_012452.2(TNFRSF13B):c.310T>C
ACTTCYGTGAGAACAAGCTCAGG
Immunoglobulin A deficiency 2,



(p.Cys104Arg)

Common variable





796052970
NM_001165963.1(SCN1A):c.1094T>C
CAAGCTYTGATACCTTCAGTTGG,
not provided



(p.Phe365Ser)
AAGCTYTGATACCTTCAGTTGGG






724159989
NC_012920.1:m.7505T>C
CCTCCAYGACTTTTTCAAAAAGG
Deafness, nonsyndromic sensorineural,





mitochondrial





796053222
NM_014191.3(SCN8A):c.4889T>C
CGTCYGATCAAAGGCGCCAAAGG,
not provided



(p.Leu1630Pro)
GTCYGATCAAAGGCGCCAAAGGG






118192127
NM_000540.2(RYR1):c.10817T>C
TACTACCYGGACCAGGTGGGTGG,
Central core disease



(p.Leu3606Pro)
ACTACCYGGACCAGGTGGGTGGG,





CTACCYGGACCAGGTGGGTGGGG






118192170
NM_000540.2(RYR1):c.14693T>C
AGGCAYTGGGGACGAGATCGAGG
Malignant hyperthermia susceptibility type 1,



(p.Ile4898Thr)

Central core disease





121917703
NM_005247.2(FGF3):c.466T>C
GTACGTGYCTGTGAACGGCAAGG,
Deafness with labyrinthine aplasia microtia and



(p.Ser156Pro)
TACGTGYCTGTGAACGGCAAGGG
microdontia (LAIVIM)





690016549
NM_005211.3(CSF1R):c.2450T>C
CCGCCYGCCTGTGAAGTGGATGG
Hereditary diffuse leukoencephalopathy h



(p.Leu817Pro)

spheroids





690016552
NM_005211.3(CSF1R):c.2566T>C
GAATCCCYACCCTGGCATCCTGG
Hereditary diffuse leukoencephalopathy with



(p.Tyr856His)

spheroids





121917738
NM_001098668.2(SFTPA2):c.593T>C
GGAGACTYCCGCTACTCAGATGG,
Idiopathic fibrosing alveolitis, chronic form



(p.Phe198Ser)
GAGACTYCCGCTACTCAGATGGG






690016559
NM_005211.3(CSF1R):c.1957T>C
AGCCYGTACCCATGGAGGTAAGG,
Hereditary diffuse leukoencephalopathy with



(p.Cys653Arg)
GCCYGTACCCATGGAGGTAAGGG
spheroids





690016560
NM_005211.3(CSFIR):c.2717T>C
GCAGAYCTGCTCCTTCCTTCAGG
Hereditary diffuse leukoencephalopathy with



(p.Ile906Thr)

spheroids





121917769
NM_003361.3(UMOD):c.376T>C
GGCCACAYGTGTCAATGTGGTGG,
Familial juvenile gout



(p.Cys126Arg)
GCCACAYGTGTCAATGTGGTGGG






121917773
NM_003361.3(UMOD):c.943T>C
ATGGCACYGCCAGTGCAAACAGG
Glomerulocystic kidney disease



(p.Cys315Arg)

with hyperuricemia and





isosthenuria





121917818
NM_007255.2(B4GALT7):c.617T>C
TGCYCTCCAAGCAGCACTACCGG
Ehlers-Danlos syndrome progeroid type



(p.Leu206Pro)







121917824
NM_021615.4(CHST6):c.827T>C
GGACCYGGCGCGGGAGCCGCTGG
Macular corneal dystrophy Type I



(p.Leu276Pro)







121917848
NM_000452.2(SLC10A2):c.728T>C
TTTCYTCTGGCTAGAATTGCTGG
Bile acid malabsorption, primary



(p.Leu243Pro)







121918006
NM_000478.4(ALPL):c.1306T>C
TGGACYATGGTGAGACCTCCAGG
Infantile hypophosphatasia



(p.Tyr436His)







121918010
NM_000478.4(ALPL):c.979T>C
CAAAGGCYTCTTCTTGCTGGTGG,
Infantile hypophosphatasia



(p.Phe327Leu)
GGCYTCTTCTTGCTGGTGGAAGG






121918088
NM_000371.3(TTR):c.400T>C
CCCCYACTCCTATTCCACCACGG




(p.Tyr134His)







121918110
NM_001042465.1(PSAP):c.1055T>C
GAAGCYGCCGAAGTCCCTGTCGG
Gaucher disease, atypical, due to saposin C



(p.Leu352Pro)

deficiency





121918137
NM_003730.4(RNASET2):c.550T>C
CCAGYGCCTTCCACCAAGCCAGG
Leukoencephalopathy, cystic,



(p.Cys184Arg)

without megalencephaly





121918191
NM_001127628.1(FBP1):c.581T>C
GGAGTYCATTTTGGTGGACAAGG
Fructose-biphosphatase deficiency



(p.Phe194Ser)







121918306
NM_006946.2(SPTBN2):c.758T>C
ACCAAGCYGCTGGATCCCGAAGG,
Spinocerebellar ataxia 5



(p.Leu253Pro)
AAGCYGCTGGATCCCGAAGGTGG,





AGCYGCTGGATCCCGAAGGTGGG






121918505
NM_000141.4(FGFR2):c.799T>C
AATGCCYCCACAGTGGTCGGAGG
Pfeiffer syndrome, Neoplasm of stomach



(p.Ser267Pro)







121918643
NM_003126.2(SPTAI):c.620T>C
GTGGAGCYGGTAGCTAAAGAAGG,
Hereditary pyropoikilocytosis, Elliptocytosis 2



(p.Leu207Pro)
TGGAGCYGGTAGCTAAAGAAGGG






121918646
NM_001024858.2(SPTB):c.604T>C
CTCCAGCYGGAAGGATGGCTTGG
Spherocytosis type 2



(p.Trp202Arg)







121918648
NM_001024858.2(SPTB):c.6055T>C
ATGCCYCTGTGGCTGAGGCGTGG




(p.Ser2019Pro)







727504166
NM_000543.4(SMPD1):c.475T>C
TGAGGCCYGTGGCCTGCTCCTGG,
Niemann-Pick disease, type A, Niemann-Pick



(p.Cys159Arg)
GAGGCCYGTGGCCTGCTCCTGGG
disease, type B





193922915
NM_000434.3(NEU1):c.1088T>C
CAGCYATGGCCAGGCCCCAGTGG
Sialidosis, type II



(p.Leu363Pro)







727504419
NM_000501.3(ELN):c.889+2T>C
CAGGYAACATCTGTCCCAGCAGG,
Supravalvar aortic stenosis




AGGYAACATCTGTCCCAGCAGGG






376395543
NM_000256.3(MYBPC3):c.26-
GAGACYGAAGGGCCAGGTGGAGG
Primary familial hypertrophic



2A>G

cardiomyopathy, Familial hypertrophic





cardiomyopathy 4, Cardiomyopathy





1169305
NM_000545.6(RNIF1A):c.1720G>A
GATGCYGGCAGGGTCCTGGCTGG,
Maturity-onset diabetes of the young, type 3



(p.Gly574Ser)
ATGCYGGCAGGGTCCTGGCTGGG,





TGCYGGCAGGGTCCTGGCTGGGG






730880130
NM_000527.4(LDLR):c.1468T>C
CTACYGGACCGACTCTGTCCTGG,
Familial hypercholesterolemia



(p.Trp490Arg)
TACYGGACCGACTCTGTCCTGGG






281860286
NM_018713.2(SLC30A10):c.500T>C
GGCGCTTYCGGGGGGCCTCAGGG
Hypermanganesemia with dystonia,



(p.Phe167Ser)

polycythemia and cirrhosis





730880306
NM_145693.2(LPIN1):c.441+2T>C
AAGGYACCGCGGGCCTCGCGCGG,
Myoglobinuria, acute recurrent, autosomal




AGGYACCGCGGGCCTCGCGCGGG
recessive





74315452
NM_000454.4(SOD1):c.338T>C
TTGCAYCATTGGCCGCACACTGG
Amyotrophic lateral sclerosis type 1



(p.Ile113Thr)







730880455
NM_000169.2(GLA):c.4IT>C
CGCGCYTGCGCTTCGCTTCCTGG
not provided



(p.Leul4Pro)







267606656
NM_054027.4(ANKH):c.1015T>C
AGCTCYGTTTCGTGATGTTTTGG
Craniometaphyseal dysplasia, autosomal



(p.Cys339Arg)

dominant





267606687
NM_033409.3(SLC52A3):c.1238T>C
AGTTACGYCAAGGTGATGCTGGG
Brown-Vialetto-Van laere syndrome



(p.Val413Ala)







267606721
NM_001928.2(CFD):c.640T>C
GGTGYGCGGGGGCGTGCTCGAGG,
Complement factor d deficiency



(p.Cys214Arg)
GTGYGCGGGGGCGTGCTCGAGGG






267606747
NM_001849.3(COL6A2):c.2329T>C
CGCCYGCGACAAGCCACAGCAGG
Ullrich congenital muscular dystrophy



(p.Cys777Arg)







431905515
NM_001044.4(SLC6A3):c.671T>C
CTGCACCYCCACCAGAGCCATGG
Infantile Parkinsonism-dystonia



(p.Leu224Pro)







267606857
NM_000180.3(GUCY2D):c.2846T>C
AGAGAYCGCCAACATGTCACTGG
Cone-rod dystrophy 6



(p.Ile949Thr)







267606880
NM_022489.3(INF2):c.125T>C
GCTGCYCCAGATGCCCTCTGTGG
Focal segmental glomerulosclerosis 5



(p.Leu42Pro)







515726191
NM_015713.4(RRM2B):c.581A>G
AACTCCTYCTACAGCAGCAAAGG
RRM2B-related mitochondrial disease



(p.Glu194Gly)







267606917
NM_004646.3(NPHS1):c.793T>C
GCTGCCGYGCGTGGCCCGAGGGG,
Finnish congenital nephrotic syndrome



(p.Cys265Arg)
CTGCCGYGCGTGGCCCGAGGGGG






267607104
NM_001199107.1(TBC1D24):c.751T>C
CAAGTTCYTCCACAAGGTGAGGG,
Myoclonic epilepsy, familial infantile



(p.Phe251Leu)
TTCYTCCACAAGGTGAGGGCCGG






267607182
NM_144631.5(ZNF513):c.1015T>C
TGGGCGCYGCATGCGAGGAGAGG,
Retinitis pigmentosa 58



(p.Cys339Arg)
CGCYGCATGCGAGGAGAGGCTGG






267607211
NM_000229.1(LCAT):c.508T>C
TATGACYGGCGGCTGGAGCCCGG
Norum disease



(p.Trp170Arg)







267607215
NM_016269.4(LEF1):c.181T>C
GAACGAGYCTGAAATCATCCCGG
Sebaceous tumors, somatic



(p.Ser61Pro}







587783580
NM_178151.2(DCX):c.683T>C
AAAAAACYCTACACTCTGGATGG
Heterotopia



(p.Leu228Pro)







587783644
NM_004004.5(GM2):c.107T>C
GATCCYCGTTGTGGCTGCAAAGG
Hearing impairment



(p.Leu36Pro)







587783653
NM_005682.6(ADGRG1):c.1460T>C
CCCTGCYCACCTGCCTTTCCTGG
Polymicrogyria, bilateral frontoparietal



(p.Leu487Pro)







587783863
NM_000252.2(MTM1):c.958T>C
GGAAYCTTTAAAAAAAGTGAAGG
Severe X-linked myotubular myopathy



(p.Ser320Pro)







267607751
NM_000249.3(MLH1):c.453+2T>C
ATCACGGYAAGAATGGTACATGG,
Hereditary Nonpolyposis Colorectal Neoplasms




TCACGGYAAGAATGGTACATGGG






119103227
NM_000411.6(HLCS):c.710T>C
CTATCYTTCTCAGGGAGGGAAGG
Holocarboxylase synthetase deficiency



(p.Leu237Pro)







119103237
NM_005787.5(ALG3):c.211T>C
GATTGACYGGAAGGCCTACATGG
Congenital disorder of glycosylation type 1D



(p.Trp7lArg)







398122806
NM_003172.3(SURF1):c.679T>C
CCACYGGCATTATCGAGACCTGG
Congenital myasthenic syndrome,



(p.Trp227Arg)

acetazolamide-responsive





80338747
NM_004525.2(LRP2):c.7564T>C
GTACCTGYACTGGGCTGACTGGG
Donnai Barrow syndrome



(p.Tyr2522His)







398122838
NM_001271723.1(FBX038):c.616T>C
TTCCTYGTATCCCAATGCTAAGG
Distal hereditary motor neuronopathy 2D



(p.Cys206Arg)







398122989
NM_014495.3(ANGPTL3):c.883T>C
ACAAAACYTCAATGAAACGTGGG
Hypobetalipoproteinemia, familial, 2



(p.Phe295Leu)







80338945
NM_004004.5(GM2):c.269T>C
GCTCCYAGTGGCCATGCACGTGG
Deafness, autosomal recessive 1A, Hearing



(p.Leu90Pro)

impairment





80338956
NM_000334.4(SCN4A):c.2078T>C
AAGATCAYTGGCAATTCAGTGGG,
Hyperkalemic Periodic Paralysis Type 1,



(p.Ile693Thr)
AGATCAYTGGCAATTCAGTGGGG,
Paramyotonia congenita of von Eulenburg




GATCAYTGGCAATTCAGTGGGGG






267608131
NM_000179.2(MSH6):c.4001+2T>C
CGGYAACTAACTAACTATAATGG
Hereditary Nonpolyposis Colorectal Neoplasms





587784573
NM_004963.3(GUCY2C):c.2782T>C
TCCCYGTGCTGCTGGAGTTGTGG,
Meconium ileus



(p.Cys928Arg)
CCCYGTGCTGCTGGAGTTGTGGG






267608511
NM_003159.2(CDKL5):c.659T>C
CCAACYTTTTACTATTCAGAAGG
Early infantile epileptic encephalopathy 2



(p.Leu220Pro)







373842615
NM_000118.3(ENG):c.1273-2A>G
CCGCCYGCGGGGATAAAGCCAGG,
Haemorrhagic telangiectasia 1




CGCCYGCGGGGATAAAGCCAGGG






185492581
NM_000335.4(SCN5A):c.376A>G
GAATCTYCACAGCCGCTCTCCGG
Brugada syndrome



(p.Lys126Glu)







200533370
NM_133499.2(SYN1):c.1699A>G
GATGYCTGACGGGTAGCCTGTGG,
Epilepsy, X-linked, with variable learning



(p.Thr567Ala)
ATGYCTGACGGGTAGCCTGTGGG
disabilities and behavior disorders, not specified





118203981
NM_148960.2(CLDN19):c.269T>C
GCTCCYGGGCTTCGTGGCCATGG
Hypomagnesemia 5, renal, with ocular



(p.Leu90Pro)

involvement





137853892
NM_001235.3(SERPINH1):c.233T>C
GTCGCYAGGGCTCGTGTCGCTGG,
Osteogenesis imperfecta type 10



(p.Leu78Pro)
TCGCYAGGGCTCGTGTCGCTGGG






118204024
NM_000263.3(NAGLU):c.142T>C
GGCCGACYTCTCCGTGTCGGTGG
Mucopolysaccharidosis,MPS-III-B





690016563
NM_005211.3(CSF1R):c.1745T>C
CAACCYGCAGTTTGGTGAGATGG
Hereditary diffuse leukoencephalopathy with



(p.Leu582Pro)

spheroids





58380626
NM_000526.4(KRT14):c.1243T>C
CGCCACCYACCGCCGCCTGCTGG,
Epidermolysis bullosa herpetiformis,



(p.Tyr415His)
CACCYACCGCCGCCTGCTGGAGG,
Dowling- Meara




ACCYACCGCCGCCTGCTGGAGGG






113994151
NM_207346.2(TSEN54):c.277T>C
TTGAAGYCTCCCGCGGTGAGCGG,
Pontocerebellar hypoplasia type 4



(p.Ser93Pro)
AAGYCTCCCGCGGTGAGCGGCGG






113994206
NM_004937.2(CTNS):c.473T>C
TGGTCYGAGCTTCGACTTCGTGG
Cystinosis



(p.Leu158Pro)







62516109
NM_000277.1(PAH):c.638T>C
CCACTTCYTGAAAAGTACTGTGG
Phenylketonuria



(p.Leu213Pro)







370011798
NM_001302946.1(TRNT1):c.668T>C
GCAAYTGCAGAAAATGCAAAAGG
Sideroblastic anemia with B-cell



(p.Ile223Thr)

immunodeficiency, periodic fevers,





and developmental delay





62517167
NM_000277.1(PAH):c.293T>C
AAGATCTYGAGGCATGACATTGG
Mild non-PKU hyperphenylalanem a



(p.Leu98Ser)







12021720
NM_001918.3(DBT):c.1150G>A
GACYCACAGAGCCCAATTTCTGG
Intermediate maple syrup urine disease type 2



(p.Gly384Ser)







104886289
NM_000495.4(COL4A5):c.4756T>C
TCCCCATYGTCCTCAGGGATGGG
Alport syndrome, X-linked recessive



(p.Cys1586Arg)







370471013
NC_012920.1:m.5559A>G
CAACYTACTGAGGGCTTTGAAGG
Leigh disease





121434215
NM_000487.5(ARSA):c.410T>C
GCCTTCCYGCCCCCCCATCAGGG
Metachromatic leukodystrophy, adult type



(p.Leu137Pro)







386134128
NM_000096.3(CP):c.1123T>C
ACACTACYACATTGCCGCTGAGG
Deficiency of ferroxidase



(p.Tyr375His)







121434275
NM_001127328.2(ACADM):c.1136T>C
GTGCAGAYACTTGGAGGCAATGG
Medium-chain acyl-coenzyme



(p.Ile379Thr)

A dehydrogenase deficiency





121434276
NM_001127328.2(ACADM):c.1136T>C
CAGCGAYGTTCAGATACTAGAGG
Medium-chain acyl-coenzyme



(p.Cys248Arg)

A dehydrogenase deficiency





121434284
NM_002225.3(IVD):c.134T>C
ATGGGCYAAGCGAGGAGCAGAGG
ISOVALERIC ACIDEMIA, TYPE I



(p.Leu45Pro)







121434334
NM_005908.3(MANBA):c.1513T>C
ATTACGYCCAGTCCTACAAATGG,
Beta-D-mannosidosis



(p.Ser505Pro)
TTACGYCCAGTCCTACAAATGGG,





TACGYCCAGTCCTACAAATGGGG






121434366
NM_000159.3(GCDH):c.883T>C
CGCCCGGYACGGCATCGCGTGGG,
Glutaric aciduria, type 1



(p.Tyr295His)
GCCCGGYACGGCATCGCGTGGGG






60715293
NM_000424.3(KRT5):c.541T>C
GTTTGCCYCCTTCATCGACAAGG
Epidermolysis bullosa herpetiformis,



(p.Ser181Pro)

Dowling-Meara





121434409
NM_001003722.1(GLE1):c.2051T>C
AAGGACAYTCCTGTCCCCAAGGG
Lethal arthrogryposis with anterior horn cell



(p.Ile684Thr)

disease





121434434
NM_001287.5(CLCN7):c.2297T>C
GGGCCYGCGGCACCTGGTGGTGG
Osteopetrosis autosomal recessive 4



(p.Leu766Pro)







121434455
NM_000466.2(PEX1):c.1991T>C
GATGACCYTGACCTCATTGCTGG
Zellweger syndrome



(p.Leu664Pro)







199422317
NM_001099274.1(TINF2):c.862T>C
CTGYTTCCCTTTAGGAATCTCGG
Aplastic anemia



(p.Phe288Leu)







104895221
NM_001065.3(TNFRSF1A):c.349T>C
CTCTTCTYGCACAGTGGACCGGG
TNF receptor-associated periodic fever



(p.Cys117Arg)

syndrome (TRAPS)





137854459
NM_000138.4(FBN1):c.4987T>C
GGGACAYGTTACAACACCGTTGG
Marfan syndrome



(p.Cys1663Arg)







387907075
NM_024027.4(COLEC11):c.505T>C
CAGCTGYCCTGCCAGGGCCGCGG,
Carnevale syndrome



(p.Ser169Pro)
AGCTGYCCTGCCAGGGCCGCGGG,





GCTGYCCTGCCAGGGCCGCGGGG,





CTGYCCTGCCAGGGCCGCGGGGG






1048095
NM_000352.4(ABCC8):c.674T>C
TGCYGTCCAAAGGCACCTACTGG
Permanent neonatal diabetes mellitus



(p.Leu225Pro)







796065347
NM_019074.3(DLL4):c.1168T>C
GAAYGTCCCCCCAACTTCACCGG
Adams-Oliver syndrome, ADAMS-



(p.Cys390Arg)

OLIVER SYNDROME 6





137852347
NM_000402.4(G6PD):c.1054T>C
AGGGYACCTGGACGACCCCACGG
Anemia, nonspherocytic hemolytic, due to



(p.Tyr352His)

G6PD deficiency





74315327
NM_213653.3(HFE2):c.302T>C
GGACCYCGCCTTCCATTCGGCGG
Hemochromatosis type 2A



(p.Leu101Pro)







137852579
NM_000044.3(AR):c.2033T>C
GTCCYGGAAGCCATTGAGCCAGG




(p.Leu678Pro)







137852636
NM_001166107.1(IIMGCS2):c.520T>C
CCCTCYTCAATGCTGCCAACTGG
mitochondria 3-hydroxy-3-methylglutaryl-



(p.Phe174Leu)

CoA synthase deficiency





137852661
NM_033163.3(FGF8):c.118T>C
TTCCCTGYTCCGGGCTGGCCGGG
Kallmann syndrome 6



(p.Phe40Leu)







121912967
NM_005215.3(DCC):c.503T>C
AGCCCAYGCCAACAATCCACTGG




(p.Met168Thr)







137852806
NM_001039523.2(CHRNA1):c.901T>C
TGTGYTCCTTCTGGTCATCGTGG
Myasthenic syndrome, congenital, fast-channel



(p.Phe301Leu)







137852850
NM_182760.3(SUMF1):c.463T>C
GGCGACYCCTTTGTCTTTGAAGG
Multiple sulfatase deficiency



(p.Ser155Pro)







137852886
NM_000158.3(GBE1):c.671T>C
AATGTACYACCAAGAATCAAAGG
Glycogen storage disease, type IV,



(p.Leu224Pro)

GLYCOGEN STORAGE DISEASE





IV, NONPROGRESSIVE HEPATIC





137852911
NM_000419.3(ITGA2B):c.641T>C
CTGGTGCYTGGGGCTCCTGGCGG
Glanzmann thrombasthenia



(p.Leu214Pro)







137852948
NM_138694.3(PKHD1):c.10658T>C
GAGCCCAYTGAAATACGCTCAGG
Polycystic kidney disease, infantile type



(p.Ile3553Thr)







137852964
NM_024960.4(PANK2):c.178T>C
ATTGACYCAGTCGGATTCAATGG




(p.Ser60Pro)







137853020
NM_006899.3(IDH3B):c.395T>C
TGCGGCYGAGGTAGGTGGTCTGG,
Retinitis pigmentosa 46



(p.Leu132Pro)
GCGGCYGAGGTAGGTGGTCTGGG






137853249
NM_033500.2(HK1):c.1550T>C
GACTTCTYGGCCCTGGATCTTGG,
Hemolytic anemia due to hexokinase deficiency



(p.Leu517Ser)
TTCTYGGCCCTGGATCTTGGAGG






137853270
NM_000444.5(PHEX):c.1664T>C
AGCYCCAGAAGCCTTTCTTTTGG
Familial X-linked hypophosphatemic vitamin



(p.Leu555Pro)

D refractory rickets





137853325
NM_003639.4(IKBKG):c.1249T>C
TGGAGYGCATTGAGTAGGGCCGG
Hypohidrotic ectodermal dysplasia with immune



(p.Cys417Arg)

deficiency, Hyper-IgM immunodeficiency, X-





linked, with hypohidrotic ectodermal dysplasia





28932769
NM_002055.4(GFAP):c.1055T>C
GGACCYGCTCAATGTCAAGCTGG
Alexander disease



(p.Leu352Pro)







397507439
NM_002769.4(PRSS1):c.116T>C
TACCAGGYGTCCCTGAATTCTGG
Hereditary pancreatitis



(p.Val39Ala)







387906446
NM_000132.3(F8):c.1729T>C
AAAGAAYCTGTAGATCAAAGAGG
Hereditary factor VIII deficiency disease



(p.Ser577Pro)







387906482
NM_000133.3(F9):c.1031T>C
ACGAACAYCTTCCTCAAATTTGG
Hereditary factor LX deficiency disease



(p.Ile344Thr)







387906508
NM_000131.4(F7):c.983T>C
GACGTYCTCTGAGAGGACGCTGG
Factor VII deficiency



(p.Phe328Ser)







387906532
NM_001040113.1(MYH11):c.3791T>C
GAAGCYGGAGGCGCAGGTGCAGG
Aortic aneurysm, familial thoracic 4



(p.Leu1264Pro)







387906658
NM_002465.3(MYBPC1):c.2566T>C
CAAACCYATATCCGCAGAGTTGG
Distal arthrogryposis type 1B



(p.Tyr856His)







387906701
NM_003491.3(NAA10):c.109T>C
TGGCCTTYCCTGGCCCCAGGTGG,
N-terminal acetyltransferase deficiency




GGCCTTYCCTGGCCCCAGGTGGG





GACTTCAYTGAGGACCAGGGTGG,






387906717
NM_000377.2(WAS):c.881T>C
ACTTCAYTGAGGACCAGGGTGGG
Severe congenital neutropenia X-linked



(p.Ile294Thr)







387906809
NM_000287.3(PEX6):c.1601T>C
CTTCYGGGCCGGGACCGTGATGG,
Peroxisome biogenesis disorder 4B



(p.Leu534Pro)
TTCYGGGCCGGGACCGTGATGGG






387906965
NM_024513.3(FYC01):c.4127T>C
CAGCCYGATCCCCATCACTGTGG
Cataract, autosomal recessive congenital 2



(p.Leu1376Pro)







387906967
NM_006147.3(IRF6):c.65T>C
GCCYCTACCCTGGGCTCATCTGG
Van der Woude syndrome, Popliteal pterygium



(p.Leu22Pro)

syndrome





387906982
NM_025132.3(WDR19):c.20T>C
TCTCACYGCTAGAAAAGACTTGG
Asphyxiating thoracic dystrophy 5



(p.Leu7Pro)







387907072
NM_032446.2(MEGF10):c.2320T>C
GGGCAGYGTACTTGCCGCACTGG
Myopathy, areflexia, respiratory distress, and



(p.Cys774Arg)

dysphagia, early-onset, Myopathy, areflexia,





respiratory distress, and dysphagia, early-onset, mild variant





137854499
NM_005502.3(ABCA1):c.6026T>C
GAGTYCTTTGCCCTTTTGAGAGG
Familial hypoalphalipoproteinemia



(p.Phe2009Ser)







387907117
NM_000196.3(HSD11B2):c.1012T>C
CCGCCGCYATTACCCCGGCCAGG,
Apparent mineralocorticoid excess



(p.Tyr338His)
CGCCGCYATTACCCCGGCCAGGG






387907170
NM_004453.3(ETFDH):c.1130T>C
CCAAAACYCACCTTTCCTGGTGG




(p.Leu377Pro)







387907205
NM_033360.3(KRAS):c.211T>C
GGACCAGYACATGAGGACTGGGG,
Cardiofaciocutaneous syndrome 2



(p.Tyr71His)
CCAGYACATGAGGACTGGGGAGG,





CAGYACATGAGGACTGGGGAGGG






387907240
NM_024110.4(CARD14):c.467T>C
CAGCAGCYGCAGGAGCACCTGGG
Pityriasis rubra pilaris



(p.Leu156Pro)







387907282
NM_152296.4(ATP1A3):c.2431T>C
TGCCATCYCACTGGCGTACGAGG
Alternating hemiplegia of childhood 2



(p.Ser811Pro)







387907361
NM_005120.2(MED12):c.3493T>C
AGGACYCTGAGCCAGGGGCCCGG
Ohdo syndrome, X-linked



(p.Ser1165Pro)







28933970
NM_006194.3(PAX9):c.62T>C
GGCCGCYGCCCAACGCCATCCGG
Tooth agenesis, selective, 3



(p.Leu21Pro)







137854472
NM_000138.4(FBN1):c.3128A>G
TGCACYTGCCGTGGGTGCAGAGG
Cardiomyopathy, not specified



(p.Lys1043Arg)







727504261
NM_000257.3(MYH7):c.2708A>G
AGCGCYCCTCAGCATCTGCCAGG




(p.Glu903Gly)







81002853
NM_000059.3(BRCA2):c.476-
ACCACYGGGGGTAAAAAAAGGGG,
Familial cancer of breast, Breast-ovarian



2A>G
TACCACYGGGGGTAAAAAAAGGG,
cancer, familial 2, Hereditary cancer-predisposing syndrome





119473032
NM_021020.3(LZTS1):c.355A>G
CCCTYCTCGGAGCCCTGTAGAGG




(p.Lys119Glu)







193922801
NM_000540.2(RYR1):c.7043A>G
TTCYCCTCCACGCTCTCGCCTGG
not provided



(p.Glu2348Gly)







36210419
NM_000218.2(KCNQ1):c.652A>G
GCCCCTYGGAGCCCACGCAGAGG
Torsades de pointes, Cardiac arrhythmia



(p.Lys218Glu)







121964989
NM_000108.4(DLD):c.1483A>G
TTCTCYAAAAGCTTCTGATAAGG
Maple syrup urine disease, type 3



(p.Arg495Gly)







28936669
NM_000095.2(COMP):c.1418A>G
ATTGYCGTCGTCGTCGTCGCAGG




(p.Asp473Gly)







28936696
NM_018488.2(TBX4):c.1592A>G
GTACYGTAAGGAAGATTCTCGGG,
Ischiopatellar dysplasia



(p.Gln531Arg)
GGTACYGTAAGGAAGATTCTCGG






121965077
NM_000137.2(FAH):c.1141A>G
TCCYGGTCTGACCATTCCCCAGG
Tyrosinemia type I



(p.Arg381Gly)







794728203
NM_000138.4(FBND:c.3344A>G
ACTCAYCAATATCTGCAAAATGG
Thoracic aortic aneurysms and aortic



(p.Asp1115Gly)

dissections





786205436
NM_003002.3(SDHD):c.275A>G
GAATAGYCCATCGCAGAGCAAGG
Fatal infantile mitochondrial cardiomyopathy



(p.Asp92Gly)







72551317
NM_000784.3(CYP27A1):c.776A>G
AGTCCACYTGGGGAGGAAGGTGG
Cholestanol storage disease



(p.Lys259Arg)







786205687
NM_016218.2(POLK):c.1385A>G
ATTCACAYTCTTCAACTTAATGG
Malignant tumor of prostate



(p.Asn462Ser)







794728280
NM_000138.4(FBN1):c.7916A>G
TGTTCAYACTGGAAGCCGGCGGG,
Thoracic aortic aneurysms and aortic



(p.Tyr2639Cys)
CTGTTCAYACTGGAAGCCGGCGG
dissections





28937317
NM_000335.4(SCN5A):c.3971A>G
GCAYTGACCACCACCTCAAGTGG
Long QT syndrome 3, Congenital long QT



(p.Asn1324Ser)

syndrome





786205854
NM_144499.2(GNAT1):c.386A>G
CGGAGYCCTTCCACAGCCGCTGG
NIGHT BLINDNESS,



(p.Asp129Gly)

CONGENITAL





104893776
NM_000539.3(RHO):c.533A>G
GGATGYACCTGAGGACAGGCAGG
Retinitis pigmentosa 4



(p.TyrI78Cys)







28937590
NM_001257342.1(BCS1L):c.232A>G
GACACYGAGGTGCTGAGTACGGG,
GRACILE syndrome



(p.Ser78Gly)
CGACACYGAGGTGCTGAGTACGG






104893866
NM_000320.2(QDPR):c.449A>G
TGCCGYACCCGATCATACCTGGG,
Dihydropteridine reductase deficiency



(p.Tyr150Cys)
ATGCCGYACCCGATCATACCTGG






587776590
NM_015629.3(PRPF31):c.527+3A>G
GACAYACCCCTGGGTGGTGGAGG,
Retinitis pigmentosa 11




GCGGACAYACCCCTGGGTGGTGG






104894015
NM_000162.3(GCK):c.64IA>G
GTAGYAGCAGGAGATCATCGTGG
Hyperinsulinemic hypoglycemia familial 3



(p.Tyr214Cys)







202247823
NM_000532.4(PCCB):c.1606A>G
ATATYTGCATGTTTTCTCCAAGG
Propionic ac dem a



(p.Asn536Asp)







104894199
NM_000073.2(CD3G):c.IA>G
CCAYGTCAGTCTCTGTCCTCCGG
Immunodeficiency 17



(p.Met1Val)







104894208
NM_001814.4(CTSC):c.857A>G
CTCCYGAGGGCTTAGGATTGGGG,
Papillon-Lef\xc3\xa8vre syndrome, Haim-



(p.Gln286Arg)
CCTCCYGAGGGCTTAGGATTGGG,
Munk syndrome




ACCTCCYGAGGGCTTAGGATTGG






104894211
NM_001814.4(CTSC):c.1040A>G
TCCTACAYAGTGGTACTCAGAGG
Papillon-Lenxc3\xa8vre



(p.Tyr347Cys)

syndrome, Periodontitis,





104894290
NM_000448.2(RAG1):c.2735A>G
CTGYACTGGCAGAGGGATTCTGG
Histiocytic medullary reticulosis



(p.Tyr912Cys)







104894354
NM_000217.2(KCNA1):c.676A>G
GCGYTTCCACGATGAAGAAGGGG,
Episodic ataxia type 1



(p.T1u.226Ala)
AGCGYTTCCACGATGAAGAAGGG,





CAGCGYTTCCACGATGAAGAAGG






104894425
NM_014239.3(EIF2B2):c.638A>G
AGTTGTCYCAATACCTGCTTTGG
Leukoencephalopathy with vanishing bite



(p.Glu213Gly)

matter, Ovarioleukodystrophy





104894450
NM_000270.3(PNP):c.383A>G
ATAYCTCCAACCTCAAACTTGGG,
Purine-nucleoside phosphorylase deficiency



(p.Asp128Gly)
GATAYCTCCAACCTCAAACTTGG






147394623
NM_024887.3(DHDDS):c.124A>G
GGCACTYCTTGGCATAGCGACGG
Retinitis pigmentosa 59



(p.Lys42Glu)







60723330
NM_005557.3(KRT16):c.374A>G
GCGGTCAYTGAGGTTCTGCATGG
Pachyonychia congenita, type 1, Palmoplantar



(p.Asn125Ser)

keratoderma, nonepidermolytic, focal





104894634
NM_030665.3(RAI1):c.4685A>G
CTGCTGCYGTCGTCGTCGCTTGG
Smith-Magenis syndrome



(p.Gln1562Arg)







104894730
NM_000363.4(TNNI3):c.532A>G
CCTYCTTCACCTGCTTGAGGTGG,
Familial restrictive cardiomyopathy 1



(p.Lys178Glu)
CCTCCTYCTTCACCTGCTTGAGG






104894816
NM_002049.3(GATA1):c.653A>G
GTCCTGYCCCTCCGCCACAGTGG
GATA-1-related thrombocytopenia



(p.Asp218Gly)

with dyserythropoiesis





794726773
NM_001165963.1(SCN1A):c.1662+3
GTGCCAYACCTGGTGTGGGGAGG
Severe myoclonic epilepsy in infancy



A>G







104894861
NM_000202.6(IDS):c.404A>G
AAAGACTYTTCCCACCGACATGG
Mucopolysaccharidosis, MPS-II



(p.Lys135Arg)







104894874
NM_000266.3(NDP):c.125A>G
TGGYGCCTCATGCAGCGTCGAGG




(p.His42Arg)







191205969
NM_002420.5(TRPM1):c.296T>C
AAGCYCTTAATATCTGTGCATGG
Congenital stationary night blindness, type 1C



(p.Leu99Pro)







794727073
NM_019109.4(ALG1):c.1188-
TAAACYGCAGAGAGAACCAAGGG,
Congenital disorder of glycosylation type 1K



2A>G
GTAAACYGCAGAGAGAACCAAG





G






281875236
NM_001004334.3(GPR179):c.659A>G
CCCACAYATCCATCTGCCTGCGG
Congenital stationary night blindness, type 1E



(p.Tyr220Cys)







28939094
NM_015915.4(ATL1):c.1222A>G
CACCCAYCTTCTTCACCCCTCGG
Spastic paraplegia 3



(p.Met408Val)







281875324
NM_005359.5(SMAD4):c.989A>G
ATCCATTYCAAAGTAAGCAATGG
Juvenile polyposis syndrome, Hereditary



(p.Glu330Gly)

cancer-predisposing syndrome





77173848
NM_000037.3(ANK1):c.-
GGGCCYGGCCCGCACGTCACAGG
Spherocytosis, type 1, autosomal recessive



108T>C







150181226
NM_001159772.1(CANT1):c.671T>C
CGTCYGTACGTGGGCGGCCTGGG,
Desbuquois syndrome



(p.Leu224Pro)
GCGTCYGTACGTGGGCGGCCTGG






397514253
NM_000041.3(APOE):c.237-
CGCCCYGCGGCCGAGAGGGCGGG,
Familial type 3 hyperlipoprote nem a



2A>G
GCGCCCYGCGGCCGAGAGGGCGG






397514348
NM_000060.3(BTD):c.278A>G
GTTCAYAGATGTCAAGGTTCTGG
Biotinidase deficiency



(p.Tyr93Cys)







397514415
NM_000060.3(BTD):c.1313A>G
GGCAYACAGCTCTTTGGATAAGG
Biotinidase deficiency



(p.Tyr438Cys)







397514501
NM_007171.3(POMT1):c.430A>G
GAGCATYCTCTGTTTCAAAGAGG
Limb-girdle muscular



(p.Asn144Asp)

dystrophy-





370382601
NM_174917.4(ACSF3):c.IA>G
GGCAGCAYTGCACTGACAGGCGG
not provided



(P.Met1Val)







72554332
NM_000531.5(OTC):c.238A>G
AAGGACTYCCCTTGCAATAAAGG
Ornithine carbamoyltransferase deficiency



(p.Lys80Glu)







397514599
NM_033109.4(PNPT1):c.1424A>G
GACTYCAGATGTAACTCTTATGG
Deafness, autosomal recessive 70



(p.Glu475Gly)







397514650
NM_000108.4(DLD):c.1444A>G
GACTCYAGCTATATCTTCACAGG
Maple syrup urine disease, type 3



(p.Arg482G1y)







397514675
NM_003156.3(STIMI):c.25IA>G
TTCCACAYCCACATCACCATTGG
Myopathy with tubular aggregates



(p.Asp84G1y)







794728378
NM_000238.3(KCNH2):c.1913A>G
ATCYTCTCTGAGTTGGTGTTGGG,
Cardiac arrhythmia



(p.Lys638Arg)
GATCYTCTCTGAGTTGGTGTTGG






397514711
NM_002163.2(IRF8):c.238A>G
AACCTCGYCTTCCAAGTGGCTGG
Autosomal dominant CD11C+/CD1C+dendritic



(p.Thr80Ala)

cell deficiency





397514729
NM_000388.3(CASR):c.85A>G
CCCCCTYCTTTTGGGCTCGCTGG
Hypocalcemia, autosomal dominant 1, with



(p.Lys29Glu)

bartter syndrome





397514743
NM_022114.3(PRDM16):c.2447A>G
GCCGCCGYTTTGGCTGGCACGGG
Left ventricular noncompaction 8



(p.Asn816Ser)







397514757
NM_005689.2(ABCB6):c.508A>G
TGGGCYGTTCCAAGACACCAGGG,
Dyschromatosis universalis hereditaria 3



(p.Ser170Gly)
GTGGGCYGTTCCAAGACACCAGG






28940313
NM_152443.2(RDH12):c.677A>G
CACTGCGYAGGTGGTGACCCCGG
Leber congenital amaurosis 13



(p.Tyr226Cys)







794728538
NM_000218.2(KCNQ1):c.1787A>G
GTCTYCTACTCGGTTCAGGCGGG,
Cardiac arrhythmia



(p.Glu596Gly)
TGTCTYCTACTCGGTTCAGGCGG






794728569
NM_000218.2(KCNQ1):c.605A>G
AGGYCTGTGGAGTGCAGGAGAGG
Cardiac arrhythmia



(p.Asp202Gly)







794728573
NM 000218.2(KCNQ1):c.1515-
GCCYGCAGTGGAGAGAGGAGAGG
Cardiac arrhythmia



2A>G







370874727
NM_003494.3(DYSF):c.3349-
CCGCCCYGGAGACACGAAGCTGG
Limb-girdle muscular dystrophy, type 2B



2A>G







794728859
NM_198056.2(SCN5A):c.2788-
ACCYGTCGAGATAATGGGTCAGG
not provided



2A>G







794728887
NM_198056.2(SCN5A):c.4462A>G
CCTCTGYCATGAAGATGTCCTGG
not provided



(p.Thr1488Ala)







28940878
NM_000372.4(TYR):c.125A>G
CTCCTGYCCCCGCTCCACGGTGG
Tyrosinase-negative oculocutaneous albinism



(p.Asp42G1y)







397515420
NM_172107.2(KCNQ2):c.1636A>G
GCAYGACACTGCAGGGGGGTGGG,
Early infantile epileptic encephalopathy 7



(p.Met546Val)
CGCAYGACACTGCAGGGGGGTGG,





AACCGCAYGACACTGCAGGGGGG






397515428
NM_001410.2(MEGF8):c.7099A>G
GACYCCCGTGAAATGATTCCCGG
Carpenter syndrome 2



(p.Ser2367Gly)







143601447
NM_201631.3(TGM5):c.122T>C
TCAACCYCACCCTGTACTTCAGG
Peeling skin syndrome, acral type



(p.Leu41Pro)







397515519
NM_000207.2(INS):c.*59A>G
GGGCYTTATTCCATCTCTCTCGG
Permanent neonatal diabetes mellitus





397515523
NM_000370.3(TTPA):c.191A>G
CAGGYCCAGATCGAAATCCCGGG,
Ataxia with vitamin E deficiency



(p.Asp64G1y)
CCAGGYCCAGATCGAAATCCCGG






397515891
NM_000256.3(MYBPC3):c.1224-
TACTTGCYGTAGAACAGAAGGGG
Familial hypertrophic cardiomyopathy 4, Cardiomyopathy



2A>G







397516082
NM_000256.3(MYBPC3):c.927-
GTCCCYGTGTCCCGCAGTCTAGG
Familial hypertrophic cardiomyopathy



2A>G

4, Cardiomyopathy





397516138
NM_000257.3(MYH7):c.2206A>G
TATCAAYGAACTGTCCCTCAGGG,
Familial hypertrophic cardiomyopathy



(p.Ile736Val)
CTATCAAYGAACTGTCCCTCAGG
1, Cardiomyopathy, not specified





1154510
NM_002150.2(HPD):c.97G>A
ATGACGYGGCCTGAATCACAGGG,
4-Alpha-hydroxyphenylpyruvate hydroxylase



(p.Ala33Thr)
AATGACGYGGCCTGAATCACAGG
deficiency





397516330
NM_000260.3(MY07A):c.6439-
ATATCCYGGGGGAGCAGAAAGGG,
Usher syndrome, type 1



2A>G
GATATCCYGGGGGAGCAGAAAGG






72556271
NM_000531.5(OTC):c.482A>G
CAGCCCAYTGATAATTGGGATGG
not provided



(p.Asn161Ser)







606231260
NM_023073.3(C5orf42):c.3290-
ATCYATCAAATACAAAAATTTGG
Orofaciodigital syndrome 6



2A>G







587777521
NM_004817.3(TJP2):c.1992-
CAGCTCYGAGAAGAAACCACGGG,
Progressive familial intrahepatic cholestasis 4



2A>G
TCAGCTCYGAGAAGAAACCACGG






730880846
NM_000257.3(MYH7):c.617A>G
CTTCYTGCTGCGGTCCCCAATGG
Cardiomyopathy



(p.Lys206Arg)







397517978
NM_206933.2(USH2A):c.12067-
TTCCCYGTAAGAAAATTAACAGG
Usher syndrome, type 2A, Retinitis pigmentosa



2A>G

39





606231409
NM_000216.2(ANOS1):c.1A>G
GCACCAYGGCTGCGGGTCGAGGG,
Kallmann syndrome 1



(p.Met1Val)
GGCACCAYGGCTGCGGGTCGAGG






80356546
NM_003334.3(UBA1):c.1639A>G
TGGCYTGTCACCCGGATATGTGG
Arthrogryposis multiplex congenita, distal,



(p.Ser547Gly)

X- linked





80356584
NM_194248.2(OTOF):c.766-
GACCYGCAGGCAGGAGAAGGGGG,
Deafness, autosomal recessive 9



2A>G
TGACCYGCAGGCAGGAGAAGGGG,





CTGACCYGCAGGCAGGAGAAGGG,





GCTGACCYGCAGGCAGGAGAAGG






730880930
NM_000257.3(MYH7):c.1615A>G
GGAACAYGCACTCCTCTTCCAGG
Cardiomyopathy



(p.Met539Val)







118203947
NM_013319.2(UBIAD1):c.355A>G
TCCYGTCATCACTCTTTTTGTGG
Schnyder crystalline conical dystrophy



(p.Arg119Gly)







60171927
NM_000526.4(KRT14):c.368A>G
GCGGTCAYTGAGGTTCTGCATGG
Epidermolysis bullosa herpetiformis,



(p.Asn123Ser)

Dowling- Meara





199422248
NM_001363.4(DKC1):c.941A>G
AATCYTGGCCCCATAGCAGATGG
Dyskeratosis congenita X-linked



(p.Lys314Arg)







72558467
NM_000531.5(OTC):c.929A>G
TCCACTYCTTCTGGCTTTCTGGG,
not provided



(p Glu310Gly)
ATCCACTYCTTCTGGCTTTCTGG






72558478
NM_000531.5(OTC):c.988A>G
ACTTTCYGTTTTCTGCCTCTGGG,
not provided



(p.Arg330G1y)
CACTTTCYGTTTTCTGCCTCTGG






118204455
NM_000505.3(F12):c.158A>G
GGTGGYACTGGAAGGGGAAGTGG




(p.Tyr53Cys)







80357477
NM_007294.3(BRCA1):c
TTGYCCTCTGTCCAGGCATCTGG
Familial cancer of breast, Breast-ovarian



(p.Asp1818Gly)

cancer, familial 1





121907908
NM_024426.4(WT1):c.1021A>G
CGCYCTCGTACCCTGTGCTGTGG
Mesothelioma



(p.Ser341Gly)







121907926
NM_000280.4(PAX6):c.1171A>G
GTGGYGCCCGAGGTGCCCATTGG
Optic nerve aplasia, bilateral



(p.Thr391Ala)







121908023
NM_024740.2(ALG9):c.860A>G
TTAYACAAAACAATGTTGAGTGG
Congenital disorder of glycosylation type 1L



(p.Tyr287Cys)







121908148
NM_001243133.1(NLRP3):c.1880A>G
ACAATYCCAGCTGGCTGGGCTGG
Familial cold urticaria



(p.Glu627Gly)







121908166
NM_006492.2(ALX3):c.608A>G
CGGYTCTGGAACCAGACCTGGGG,
Frontonasal dysplasia



(p.Asn203Ser)
GCGGYTCTGGAACCAGACCTGGG,





TGCGGYTCTGGAACCAGACCTGG






121908184
NM_020451.2(SEPN1):c.1A>G
CCCAYGGCTGCGGCTGGCGGCGG,
Eichsfeld type congenital muscular dystrophy



(p.Met1Val)
CGGCCCAYGGCTGCGGCTGGCGG






121908258
NM_130468.3(CHST14):c.878A>G
AAGTCAYAGTGCACGGCACAAGG
Ehlers-Danlos syndrome, musculocontractural



(p.Tyr293Cys)

type





121908383
NM_001128425.1(MUTYH):c.1241A>G
AAGCYGCTCTGAGGGCTCCCAGG
Neoplasm of stomach



(p.Gln414Arg)







121908580
NM_004328.4(BCS1L):c.148A>G
GTGYGATCATGTAATGGCGCCGG
Mitochondrial complex III deficiency



(p.Thr50Ala)







121908584
NM_016417.2(GLRX5):c.294A>G
CCTGACCYTGTCGGAGCTCCGGG
Anemia, sideroblastic, pyridoxine-refractory,



(p.Gln98=)

autosomal recessive





121908635
NM_022817.2(PER2):c.1984A>G
GCCACACYCTCTGCCTTGCCCGG
Advanced sleep phase syndrome, familial



(p.Ser662Gly)







121908655
NM_003839.3(TNERSF11A):c.508A>G
GGGTCYGCATTTGTCCGTGGAGG
Osteopetrosis autosomal recessive 7



(p.Arg170Gly)




29001653
NM_000539.3(RHO):c.886A>G
CGCTCTYGGCAAAGAACGCTGGG,
Retinitis pigmentosa 4



(p.Lys296Glu)
GCGCTCTYGGCAAAGAACGCTGG






56307355
NM_006502.2(POLH):c.1603A>G
AGACTTTYCTGCTTAAAGAAGGG
Xeroderma pigmentosum, variant type



(p.Lys535Glu)







121908919
NM_002977.3(SCN9A):c.1964A>G
CCTTTTCYTGTGTATTTGATTGG
Generalized epilepsy with febrile seizures plus,



(p.Lys655Arg)

type 7 not specified





121908939
NM_006892.3(DNMT3B):c.2450A>G
GACACGYCTGTGTAGTGCACAGG
Centromeric instability of chromosomes 1,9 and



(p.Asp817Gly)

16 and immunodeficiency





121909088
NM_001005360.2(DNM2):c.1684A>G
ACTYCTTCTCTTTCTCCTGAGGG,
Charcot-Marie-Tooth disease, dominant



(p.Lys562Glu)
TACTYCTTCTCTTTCTCCTGAGG
intermediate b, with neutropenia





120074112
NM_000483.4(APOC2):c.1A>G
GCCCAYAGTGTCCAGAGACCTGG
Apolipoprotein C2 deficiency



(p.Met1Val)







121909239
NM_000314.6(PTEN):c.755A>G
ATAYCACCACACACAGGTAACGG
Macrocephaly/autism syndrome



(p.Asp252G1y)







121909251
NM_198217.2(ING1):c.515A>G
TGGYTGCACAGACAGTACGTGGG,
Squamous cell carcinoma of the head and neck



(p.Asn172Ser)
CTGGYTGCACAGACAGTACGTGG






121909396
NM_001174089.1(SLC4A11):c.2518A>G
GATCAYCTTCATGTAGGGCAGGG,
Corneal dystrophy and perceptive deafness



(p.Met840Val)
AGATCAYCTTCATGTAGGGCAGG






121909533
NM_000034.3(ALD0A):c.386A>G
CCAYCCAACCCTAAGAGAAGAGG
HNSHA due to aldolase A deficiency



(p.Asp129Gly)







128627255
NM_004006.2(DMD):c.835A>G
TGACCGYGATCTGCAGAGAAGGG,
Dilated cardiomyopathy 3B



(p.Thr279Ala)
CTGACCGYGATCTGCAGAGAAGG






116929575
NM_001085.4(SERPINA3):c.1240A>G
GCTCAYGAAGAAGATGTTCTGGG,




(p.Met414Val)
TGCTCAYGAAGAAGATGTTCTGG






61748392
NM_004992.3(MECP2):c.410A>G
CAACYCCACTTTAGAGCGAAAGG
Mental retardation, X-linked, syndromic 13



(p.Glu137Gly)







61748906
NM_001005741.2(GBA):c.667T>C
CCCACTYGGCTCAAGACCAATGG
Gaucher disease, type 1



(p.Trp223Arg)







199473024
NM_000238.3(KCNH2):c.3118A>G
CTGCYCTCCACGTCGCCCCGGGG,
Sudden infant death syndrome



(p.Ser1040Gly)
CCTGCYCTCCACGTCGCCCCGGG,





GCCTGCYCTCCACGTCGCCCCGG






794728365
NM_000238.3(KCNH2):c.1129-
GGACCYGCACCCGGGGAAGGCGG
Cardiac arrhythmia



2A>G










72556293
NM_000531.5(OTC):c.548A>G
AGAGCTAYAGTGTTCCTAAAAGG
not provided



(p.Tyr183Cys)







111033244
NM_000441.1(SLC26A4):c.1151A>G
TGAATYCCTAAGGAAGAGACTGG
Pendred syndrome, Enlarged vestibular



(p.Glu384Gly)

aqueduct syndrome





111033415
NM_000260.3(MY07A):c.1344-
AGCYGCAGGGGCACAGGGATGGG,
Usher syndrome, type 1



2A>G
AAGCYGCAGGGGCACAGGGATGG






121912439
NM_000454.4(SOD1):c.302A>G
AGAATCTYCAATAGACACATCGG
Amyotrophic lateral sclerosis type 1



(p.Glu101Gly)







111033567
NM_002769.4(PRSS1):c.68A>G
ATCYTGTCATCATCATCAAAGGG,
Hereditarypancreatitis



(p.Lys23Arg)
GATCYTGTCATCATCATCAAAG





G






121912565
NM_000901.4(NR3C2):c.2327A>G
TCATCYGTTTGCCTGCTAAGCGG
Pseudohypoaldosteronism type 1 autosomal



(p.Gln776Arg)

dominant





121912574
NM_000901.4(NR3C2):c.2915A>G
CCGACYCCACCTTGGGCAGCTGG
Pseudohypoaldosteronism type 1 autosomal



(p.Glu972Gly)

dominant





121912589
NM_001173464.1(KIF21A):c.2839A>G
ATTCAYATCTGCCTCCATGTTGG
Fibrosis of extraocular muscles, congenital, 1



(p.Met947Val)







111033661
NM_000155.3(GALT):c.253-
ATTCACCYACCGACAAGGATAGG
Deficiency of UDPglucose-hexose-1-phosphate



2A>G

uridylyltransferase





111033669
NM_000155.3(GALT):c.290A>G
GAAGTCGYTGTCAAACAGGAAGG
Deficiency of UDPglucose-hexose-1-phosphate



(p.Asn97Ser)

uridylyltransferase





111033682
NM_000155.3(GALT):c.379A>G
TGACCTYACTGGGTGGTGACGGG,
Deficiency of UDPglucose-hexose-1-phosphate



(p.Lys127Glu)
ATGACCTYACTGGGTGGTGACGG
uridylyltransferase





111033786
NM_000155.3(GALT):c.950A>G
CAGCYGCCAATGGTTCCAGTTGG
Deficiency of UDPglucose-hexose-1-phosphate



(p.Gln317Arg)

uridylyltransferase





121912765
NM_001202.3(BMP4):c.278A>G
CCTCCYCCCCAGACTGAAGCCGG
Microphthalmia syndromic 6



(p.Glu93Gly)







121912856
NM_000094.3(COL7A1):c.425A>G
CACCYTGGGGACACCAGGTCGGG,
Epidermolysis bullosa dystrophica inversa,



(p.Lys142Arg)
TCACCYTGGGGACACCAGGTCGG
autosomal recessive





199474715
NM_152263.3(TPM3):c.505A>G
CCAACTYACGAGCCACCTACAGG
Congenital myopathy with fiber



(p.Lys169Glu)

type disproportion





199474718
NM_152263.3(TPM3):c.733A>G
ATCYCTCAGCAAACTCAGCACGG
Congenital myopathy with fiber



(p.Arg245Gly)

type disproportion





121912895
NM_001844.4(COL2A1):c.2974A>G
CCTCYCTCACCACGTTGCCCAGG
Spondyloepimetaphyseal dysplasia Strudwick



(p.Arg992Gly)

type





121913074
NM_000129.3(F13A1):c.851A>G
ATAGGCAYAGATATTGTCCCAGG
Factor xiii, a subunit, deficiency of



(p.Tyr284Cys)







121913145
NM_000208.2(INSR):c.707A>G
GCTGYGGCAACAGAGGCCTTCGG
Leprechaunism syndrome



(p.His236Arg)







312262745
NM_025137.3(SPG11):c.2608A>G
ACTTAYCCTGGGGAGAAGGATGG
Spastic paraplegia 11, autosomal recessive



(p.Ile870Val)







121913682
NM_000222.2(KIT):c.2459A>G
AGAAYCATTCTTGATGTCTCTGG
Mast cell disease, systemic



(p.Asp820Gly)







587776757
NM_000151.3(G6PC):c.230+4A>G
GTTCYTACCACTTAAAGACGAGG
Glycogen storage disease type 1A





61752063
NM_000330.3(RS1):c.286T>C
TTCTTCGYGGACTGCAAACAAGG
Juvenile retinoschisis



(p.Trp96Arg)







367543065
NM_024549.5(TCTN1):c.221-
AGCAACYGCAGAAAAAAGAGGGG,
Joubert syndrome 13



2A>G
CAGCAACYGCAGAAAAAAGAGG





G






5030773
NM_000894.2(LHB):c.221A>G
CCACCYGAGGCAGGGGCGGCAGG
Isolated lutropin deficiency



(p.Gln74Arg)







199476092
NM_000264.3(PTCH1):c.2479A>G
CGTTACYGAAACTCCTGTGTAGG
Gorlin syndrome, Holoprosencephaly 7, not



(p.Ser827Gly)

specified





398123158
NM_000117.2(EMD):c.450-
CGTTCCCYGAGGCAAAAGAGGGG
not provided



2A>G







199476103
RMRP:n.71A>G
ACTTYCCCCTAGGCGGAAAGGGG,
Metaphyseal chondrodysplasia, McKusick type,




GACTTYCCCCTAGGCGGAAAGGG,
Metaphyseal dysplasia without hypotrichosis




GGACTTYCCCCTAGGCGGAAAGG






5030856
NM_000277.1(PAH):c.1169A>G
CTCYCTGCCACGTAATACAGGGG,
Phenylketonuria, Hyperphenylalaninemia, non-



(p.Glu390Gly)
ACTCYCTGCCACGTAATACAGGG,
Pku




AACTCYCTGCCACGTAATACAGG






5030860
NM_000277.1(PAH):c.1241A>G
GGGTCGYAGCGAACTGAGAAGGG,
Phenylketonuria, Hyperphenylalaninem a non-



(p.Tyr414Cys)
TGGGTCGYAGCGAACTGAGAAGG
Pku





587777055
NM_020988.2(GNAO1):c.521A>G
GGATGYCCTGCTCGGTGGGCTGG
Early infantile epileptic encephalopathy 17



(p.Asp174Gly)







587777223
NM_024301.4(FKRP):c.1A>G
CCGCAYGGGGCCGAAGTCTGGGG,
Congenital muscular dystrophy-dystroglycanopathy



(p.Met1Val)
GCCGCAYGGGGCCGAAGTCTGGG,
with brain and eye anomalies type AS




AGCCGCAYGGGGCCGAAGTCTGG






587777479
NM_003108.3(S0X11):c.347A>G
GTACTTGYAGTCGGGGTAGTCGG
Mental retardation, autosomal dominant 27



(p.Tyr116Cys)







587777496
NM_020435.3(GJC2):c.-170A>G
TTGYTCCCCCCTCGGCCTCAGGG,
Leukodystrophy, hypomyelinating, 2




ATTGYTCCCCCCTCGGCCTCAGG






587777507
NM_022552.4(DNMT3A):c.1943T>C
CTCCYGGTGCTGAAGGACTTGGG,
Tatton-Brown-rahman syndrome



(p.Leu648Pro)
GCTCCYGGTGCTGAAGGACTTGG






587777557
NM_018400.3(SCN3B):c.482T>C
AATCAYGATGTACATCCTTCTGG
Atrial fibrillation, familial, 16



(p.Met161Thr)







587777569
NM_001030001.2(RPS29):c.149T>C
GATAYCGGTTTCATTAAGGTAGG
Diamond-Blackfan anemia 13



(p.Ile50Thr)







587777657
NM_153334.6(SCARF2):c.190T>C
CCACGYGCTGCGCTGGCTGGAGG
Marden Walker like syndrome



(p.Cys64Arg)







587777689
NM_005726.5(TSFM):c.57+4A>G
ACTTCYCACCGGGTAGCTCCCGG
Combined oxidative phosphorylation deficiency 3





796052005
NM_000255.3(MUT):c.329A>G
GCAYACTGGCGGATGGTCCAGGG,
not provided



(p.Tyr110Cys)
AGCAYACTGGCGGATGGTCCAGG






587777809
NM_144596.3(TTC8):c.115-
GTTCCYGGAAAGCATTAAGAAGG
Retinitis pigmentosa 51



2A>G







587777878
NM_000166.5(GJB1):c.580A>G
TAGCAYGAAGACGGTGAAGACGG
X-linked hereditary motor and sensory



(p.Met194Val)

neuropathy





74315420
NM_001029871.3(RSPO4):c.194A>G
CGTACYGGCGGATGCCTTCCCGG
Anonychia



(p.Gln65Arg)







180177219
NM_000030.2(AGXT):c.424-2A>G
AGGCCCYGAGGAAGCAGGGACGG
Primary hyperoxaluria, type I



(p.Gly_142Gln145del)







367610201
NM_002693.2(POLG):c.1808T>C
CTCAYGGCACTTACCTGGGATGG
not provided



(p.Met603Thr)







180177319
NM_012203.1(GRHPR):c.84-
TCACAGCYGCGGGGAAAGGGAGG
Primary hyperoxaluria, type II



2A>G







796052068
NM_000030.2(AGXT):c.777-
GGTACCYGGAAGACACGAGGGGG,
Primary hyperoxaluria, type I



2A>G
TGGTACCYGGAAGACACGAGGGG






61754010
NM_000552.3(VWF):c.1583A>G
TGCCAYTGTAATTCCCACACAGG
von Willebrand disease, type 2a



(p.Asn528Ser)







587778866
NM_000321.2(RB1):c.1927A>G
ATTYCAATGGCTTCTGGGTCTGG
Retinoblastoma



(p.Lys643Glu)







74435397
NM_006331.7(EMG1):c.257A>G
ATAYCTGGCCGCGCTTCCCCAGG
Bowen-Conradi syndrome



(p.Asp86G1y)







796052527
NM_000156.5(GAMT):c.1A>G
CGCTCAYGCTGCAGGCTGGACGG
not provided



(p.Met1Val)







796052637
NM_172107.2(KCNQ2):c.848A>G
GTACYTGTCCCCGTAGCCAATGG
not provided



(p.Lys283Arg)







724159963
NM_032228.5(FARH:c.1094A>G
GATAYCATACAGGAATGCTGGGG,
Peroxisomal fatty acyl-coa reductase 1 disorder



(p.Asp365Gly)
AGATAYCATACAGGAATGCTGGG,





TAGATAYCATACAGGAATGCTGG






587779722
NM_000090.3(COL3A1):c.1762-2A>G
CACCCYAAAGAAGAAGTGGTCGG
Ehlers-Danlos syndrome, type 4



(p.Gly588_Gln605del)







118192102
m.8296A>G
TTTACAGYGGGCTCTAGAGGGGG
Diabetes-deafness syndrome maternally





transmitted





727502787
NM_001077494.3(NEKB2):c.2594A>G
CTGYCTTCCTTCACCTCTGCTGG
Common variable immunodeficiency 10



(p.Asp865Gly)







727503036
NM_000117.2(EMD):c.266-
AGCCYTGGGAAGGGGGGCAGCGG
Emery-Dreifuss muscular dystrophy 1, X-linked



2A>G







690016544
NM_005861.3(STUB1):c.194A>G
GGCCCGGYTGGTGTAATACACGG
Spinocerebellar ataxia, autosomal recessive 16



(p.Asn65Ser)







690016554
NM_005211.3(CSF1R):c.2655-
GTATCYGGGAGATAGGACAGAGG
Hereditary diffuse leukoencephalopathy with



2A>G

spheroids





118192185
NM_172107.2(KCNQ2):c.1A>G
GCACCAYGGTGCCTGGCGGGAGG
Benign familial neonatal seizures 1



(p.Met1Val)







121917869
NM_012064.3(MIP):c.401A>G
AGATCYCCACTGTGGTTGCCTGG
Cataract 15, multiple types



(p.Glu134Gly)







121918014
NM_000478.4(ALPL):c.1250A>G
AGGCCCAYTGCCATACAGGATGG
Infantile hypophosphatasia



(p.Asn417Ser)







121918036
NM_000174.4(GP9):c.110A>G
GCAGYCCACCCACAGCCCCATGG
Bernard-Soulier syndrome type C



(p.Asp37G1y)







121918089
NM_000371.3(TTR):c.379A>G
CGGCAAYGGTGTAGCGGCGGGGG,
Amyloidogenic transthyretin amyloidosis



(p.Ile127Val)
GCGGCAAYGGTGTAGCGGCGGGG






121918121
NM_000823.3(GHRHR):c.985A>G
CGACTYGGAGAGACGCCTGCAGG
Isolated growth hormone deficiency type 1B



(p.Lys329Glu)







121918333
NM_015335.4(MED13L):c.6068A>G
ATATCAYCTAGAGGGAAGGGGGG,
Transposition of great arteries



(p.Asp2023Gly)
CATATCAYCTAGAGGGAAGGGGG






121918605
NM_001035.2(RYR2):c.12602A>G
CGCCAGCYGCATTTCAAAGATGG
Catecholaminergic polymorphic



(p.Gln4201Arg)

ventricular tachycardia





587781262
NM_002764.3(PRPS1):c.343A>G
TAGCAYATTTGCAACAAGCTTGG
Charcot-Marie-Tooth disease, X-linked



(p.Met115Val)

recessive, type 5, Deafness, high-frequency





sensorineural, X-linked





121918608
NM_001161766.1(AHCY):c.344A>G
GCGGGYACTTGGTGTGGATGAGG
Hypermethioninemia with s-adenosylhomocysteine



(p.Tyr115Cys)

hydrolase deficiency





121918613
NM_000702.3(ATP1A2):c.1033A>G
CTGYCAGGGTCAGGCACACCTGG
Familial hemiplegic migraine type 2



(p.Thr345Ala)







587781339
NM_000535.5(PMS2):c.904-
GCAGACCYGCACAAAATACAAGG
Hereditary cancer-predisposing syndrome



2A>G







121918691
NM_001128177.1(THRB):c.1324A>G
CTTCAYGTGCAGGAAGCGGCTGG
Thyroid hormone resistance, generalized,



(p.Met442Val)

autosomal dominant





121918692
NM_001128177.1(THRB):c.1327A>G
CCACCTYCATGTGCAGGAAGCGG
Thyroid hormone resistance, generalized,



(p.Lys443Glu)

autosomal dominant





727504333
NM_000256.3(MYBPC3):c.2906-
CCGTTCYGTGGGTATAGAGTGGG,
Familial hypertrophic cardiomyopathy 4



2A>G
GCCGTTCYGTGGGTATAGAGTGG






730880805
NM_006204.3(PDE6C):c.1483-
CTTTCYGTTGAAATAAGGATGGG,
Achromatopsia 5



2A>G
TCTTTCYGTTGAAATAAGGATGG






281860296
NM_000551.3(VHL):c.586A>T
GGTCTTYCTGCACATTTGGGTGG
Von Hippel-Lindau syndrome



(p.Lys196Ter)







730880444
NM_000169.2(GLA):c.370-
GTGAACCYGAAATGAGAGGGAGG
not provided



2A>G







756328339
NM_000256.3(MYBPC3):c.1227-
GTACCYGGGTGGGGGCCGCAGGG,
Familial hypertrophic cardiomyopathy



2A>G
TGTACCYGGGTGGGGGCCGCAGG
4, Cardiomyopathy





267606643
NM_013411.4(AK2):c.494A>G
TCAYCTTTCATGGGCTCTTTTGG
Reticular dysgenesis



(p.Asp165Gly)







267606705
NM_005188.3(CBL):c.1144A>G
TATTTYACATAGTTGGAATGTGG
Noonan syndrome-like disorder with or without



(p.Lys382Glu)

juvenile myelomonocytic leukemia





62642934
NM_000277.1(PAH):c.916A>G
GGCCAAYTTCCTGTAATTGGGGG,
Phenylketonuria, Hyperphenylalaninemia, non-



(p.Ile306Val)
AGGCCAAYTTCCTGTAATTGGGG
Pku





267606782
NM_000117.2(EMD):c.1A>G
TCCAYGGCGGGTGCGGGCTCAGG
Emery-Dreifuss muscular dystrophy, X-linked



(p.Met1Val)







267606820
NM_014053.3(FLVCR1):c.361A>G
AGGCGTYGACCAGCGAGTACAGG
Posterior column ataxia with



(p.Asn121Asp)

retinitis pigmentosa









In some embodiments, any of the base editors provided herein may be used to treat a disease or disorder. For example, any base editors provided herein may be used to correct one or more mutations associated with any of the diseases or disorders provided herein. Exemplary diseases or disorders that may be treated include, without limitation, 3-Methylglutaconic aciduria type 2, 46,XY gonadal dysgenesis, 4-Alpha-hydroxyphenylpyruvate hydroxylase deficiency, 6-pyruvoyl-tetrahydropterin synthase deficiency, achromatopsia, Acid-labile subunit deficiency, Acrodysostosis, acroerythrokeratoderma, ACTH resistance, ACTH-independent macronodular adrenal hyperplasia, Activated PI3K-delta syndrome, Acute intermittent porphyria, Acute myeloid leukemia, Adams-Oliver syndrome 1/5/6, Adenylosuccinate lyase deficiency, Adrenoleukodystrophy, Adult neuronal ceroid lipofuscinosis, Adult onset ataxia with oculomotor apraxia, Advanced sleep phase syndrome, Age-related macular degeneration, Alagille syndrome, Alexander disease, Allan-Herndon-Dudley syndrome, Alport syndrome, X-linked recessive, Alternating hemiplegia of childhood, Alveolar capillary dysplasia with misalignment of pulmonary veins, Amelogenesis imperfecta, Amyloidogenic transthyretin amyloidosis, Amyotrophic lateral sclerosis, Anemia (nonspherocytic hemolytic, due to G6PD deficiency), Anemia (sideroblastic, pyridoxine-refractory, autosomal recessive), Anonychia, Antithrombin III deficiency, Aortic aneurysm, Aplastic anemia, Apolipoprotein C2 deficiency, Apparent mineralocorticoid excess, Aromatase deficiency, Arrhythmogenic right ventricular cardiomyopathy, Familial hypertrophic cardiomyopathy, Hypertrophic cardiomyopathy, Arthrogryposis multiplex congenital, Aspartylglycosaminuria, Asphyxiating thoracic dystrophy, Ataxia with vitamin E deficiency, Ataxia (spastic), Atrial fibrillation, Atrial septal defect, atypical hemolytic-uremic syndrome, autosomal dominant CD11C+/CD1C+ dendritic cell deficiency, Autosomal dominant progressive external ophthalmoplegia with mitochondrial DNA deletions, Baraitser-Winter syndrome, Bartter syndrome, Basa ganglia calcification, Beckwith-Wiedemann syndrome, Benign familial neonatal seizures, Benign scapuloperoneal muscular dystrophy, Bernard Soulier syndrome, Beta thalassemia intermedia, Beta-D-mannosidosis, Bietti crystalline corneoretinal dystrophy, Bile acid malabsorption, Biotinidase deficiency, Borjeson-Forssman-Lehmann syndrome, Boucher Neuhauser syndrome, Bowen-Conradi syndrome, Brachydactyly, Brown-Vialetto-Van laere syndrome, Brugada syndrome, Cardiac arrhythmia, Cardiofaciocutaneous syndrome, Cardiomyopathy, Carnevale syndrome, Carnitine palmitoyltransferase II deficiency, Carpenter syndrome, Cataract, Catecholaminergic polymorphic ventricular tachycardia, Central core disease, Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency, Cerebral autosomal dominant arteriopathy, Cerebro-oculo-facio-skeletal syndrome, Ceroid lipofuscinosis, Charcot-Marie-Tooth disease, Cholestanol storage disease, Chondrocalcinosis, Chondrodysplasia, Chronic progressive multiple sclerosis, Coenzyme Q10 deficiency, Cohen syndrome, Combined deficiency of factor V and factor VIII, Combined immunodeficiency, Combined oxidative phosphorylation deficiency, Combined partial 17-alpha-hydroxylase/17,20-lyase deficiency, Complement factor d deficiency, Complete combined 17-alpha-hydroxylase/17,20-lyase deficiency, Cone-rod dystrophy, Congenital contractural arachnodactyly, Congenital disorder of glycosylation, Congenital lipomatous overgrowth, Neoplasm of ovary, PIK3CA Related Overgrowth Spectrum, Congenital long QT syndrome, Congenital muscular dystrophy, Congenital muscular hypertrophy-cerebral syndrome, Congenital myasthenic syndrome, Congenital myopathy with fiber type disproportion, Eichsfeld type congenital muscular dystrophy, Congenital stationary night blindness, Corneal dystrophy, Cornelia de Lange syndrome, Craniometaphyseal dysplasia, Crigler Najjar syndrome, Crouzon syndrome, Cutis laxa with osteodystrophy, Cyanosis, Cystic fibrosis, Cystinosis, Cytochrome-c oxidase deficiency, Mitochondrial complex I deficiency, D-2-hydroxyglutaric aciduria, Danon disease, Deafness with labyrinthine aplasia microtia and microdontia (LAMM), Deafness, Deficiency of acetyl-CoA acetyltransferase, Deficiency of ferroxidase, Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase, Dejerine-Sottas disease, Desbuquois syndrome, DFNA, Diabetes mellitus type 2, Diabetes-deafness syndrome, Diamond-Blackfan anemia, Diastrophic dysplasia, Dihydropteridine reductase deficiency, Dihydropyrimidinase deficiency, Dilated cardiomyopathy, Disseminated atypical mycobacterial infection, Distal arthrogryposis, Distal hereditary motor neuronopathy, Donnai Barrow syndrome, Duchenne muscular dystrophy, Becker muscular dystrophy, Dyschromatosis universalis hereditaria, Dyskeratosis congenital, Dystonia, Early infantile epileptic encephalopathy, Ehlers-Danlos syndrome, Eichsfeld type congenital muscular dystrophy, Emery-Dreifuss muscular dystrophy, Enamel-renal syndrome, Epidermolysis bullosa dystrophica inversa, Epidermolysis bullosa herpetiformis, Epilepsy, Episodic ataxia, Erythrokeratodermia variabilis, Erythropoietic protoporphyria, Exercise intolerance, Exudative vitreoretinopathy, Fabry disease, Factor V deficiency, Factor VII deficiency, Factor xiii deficiency, Familial adenomatous polyposis, breast cancer, ovarian cancer, cold urticarial, chronic infantile neurological, cutaneous and articular syndrome, hemiplegic migraine, hypercholesterolemia, hypertrophic cardiomyopathy, hypoalphalipoproteinemia, hypokalemia-hypomagnesemia, juvenile gout, hyperlipoproteinemia, visceral amyloidosis, hypophosphatemic vitamin D refractory rickets, FG syndrome, Fibrosis of extraocular muscles, Finnish congenital nephrotic syndrome, focal epilepsy, Focal segmental glomerulosclerosis, Frontonasal dysplasia, Frontotemporal dementia, Fructose-biphosphatase deficiency, Gamstorp-Wohlfart syndrome, Ganglioside sialidase deficiency, GATA-1-related thrombocytopenia, Gaucher disease, Giant axonal neuropathy, Glanzmann thrombasthenia, Glomerulocystic kidney disease, Glomerulopathy, Glucocorticoid resistance, Glucose-6-phosphate transport defect, Glutaric aciduria, Glycogen storage disease, Gorlin syndrome, Holoprosencephaly, GRACILE syndrome, Haemorrhagic telangiectasia, Hemochromatosis, Hemoglobin H disease, Hemolytic anemia, Hemophagocytic lymphohistiocytosis, Carcinoma of colon, Myhre syndrome, leukoencephalopathy, Hereditary factor IX deficiency disease, Hereditary factor VIII deficiency disease, Hereditary factor XI deficiency disease, Hereditary fructosuria, Hereditary Nonpolyposis Colorectal Neoplasm, Hereditary pancreatitis, Hereditary pyropoikilocytosis, Elliptocytosis, Heterotaxy, Heterotopia, Histiocytic medullary reticulosis, Histiocytosis-lymphadenopathy plus syndrome, HNSHA due to aldolase A deficiency, Holocarboxylase synthetase deficiency, Homocysteinemia, Howel-Evans syndrome, Hydatidiform mole, Hypercalciuric hypercalcemia, Hyperimmunoglobulin D, Mevalonic aciduria, Hyperinsulinemic hypoglycemia, Hyperkalemic Periodic Paralysis, Paramyotonia congenita of von Eulenburg, Hyperlipoproteinemia, Hypermanganesemia, Hypermethioninemia, Hyperphosphatasemia, Hypertension, hypomagnesemia, Hypobetalipoproteinemia, Hypocalcemia, Hypogonadotropic hypogonadism, Hypogonadotropic hypogonadism, Hypohidrotic ectodermal dysplasia, Hyper-IgM immunodeficiency, Hypohidrotic X-linked ectodermal dysplasia, Hypomagnesemia, Hypoparathyroidism, Idiopathic fibrosing alveolitis, Immunodeficiency, Immunoglobulin A deficiency, Infantile hypophosphatasia, Infantile Parkinsonism-dystonia, Insulin-dependent diabetes mellitus, Intermediate maple syrup urine disease, Ischiopatellar dysplasia, Islet cell hyperplasia, Isolated growth hormone deficiency, Isolated lutropin deficiency, Isovaleric acidemia, Joubert syndrome, Juvenile polyposis syndrome, Juvenile retinoschisis, Kallmann syndrome, Kartagener syndrome, Kugelberg-Welander disease, Lattice corneal dystrophy, Leber congenital amaurosis, Leber optic atrophy, Left ventricular noncompaction, Leigh disease, Mitochondrial complex I deficiency, Leprechaunism syndrome, Arthrogryposis, Anterior horn cell disease, Leukocyte adhesion deficiency, Leukodystrophy, Leukoencephalopathy, Ovarioleukodystrophy, L-ferritin deficiency, Li-Fraumeni syndrome, Limb-girdle muscular dystrophy-dystroglycanopathy, Loeys-Dietz syndrome, Long QT syndrome, Macrocephaly/autism syndrome, Macular corneal dystrophy, Macular dystrophy, Malignant hyperthermia susceptibility, Malignant tumor of prostate, Maple syrup urine disease, Marden Walker like syndrome, Marfan syndrome, Marie Unna hereditary hypotrichosis, Mast cell disease, Meconium ileus, Medium-chain acyl-coenzyme A dehydrogenase deficiency, Melnick-Fraser syndrome, Mental retardation, Merosin deficient congenital muscular dystrophy, Mesothelioma, Metachromatic leukodystrophy, Metaphyseal chondrodysplasia, Methemoglobinemia, methylmalonic aciduria, homocystinuria, Microcephaly, chorioretinopathy, lymphedema, Microphthalmia, Mild non-PKU hyperphenylalanemia, Mitchell-Riley syndrome, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency, Mitochondrial complex I deficiency, Mitochondrial complex III deficiency, Mitochondrial myopathy, Mucolipidosis III, Mucopolysaccharidosis, Multiple sulfatase deficiency, Myasthenic syndrome, Mycobacterium tuberculosis, Myeloperoxidase deficiency, Myhre syndrome, Myoclonic epilepsy, Myofibrillar myopathy, Myoglobinuria, Myopathy, Myopia, Myotonia congenital, Navajo neurohepatopathy, Nemaline myopathy, Neoplasm of stomach, Nephrogenic diabetes insipidus, Nephronophthisis, Nephrotic syndrome, Neurofibromatosis, Neutral lipid storage disease, Niemann-Pick disease, Non-ketotic hyperglycinemia, Noonan syndrome, Noonan syndrome-like disorder, Norum disease, Macular degeneration, N-terminal acetyltransferase deficiency, Oculocutaneous albinism, Oculodentodigital dysplasia, Ohdo syndrome, Optic nerve aplasia, Ornithine carbamoyltransferase deficiency, Orofaciodigital syndrome, Osteogenesis imperfecta, Osteopetrosis, Ovarian dysgenesis, Pachyonychia, Palmoplantar keratoderma, nonepidermolytic, Papillon-Lefxc3xa8vre syndrome, Haim-Munk syndrome, Periodontitis, Peeling skin syndrome, Pendred syndrome, Peroxisomal fatty acyl-coa reductase 1 disorder, Peroxisome biogenesis disorder, Pfeiffer syndrome, Phenylketonuria, Phenylketonuria, Hyperphenylalaninemia, non-PKU, Pituitary hormone deficiency, Pityriasis rubra pilaris, Polyarteritis nodosa, Polycystic kidney disease, Polycystic lipomembranous osteodysplasia, Polymicrogyria, Pontocerebellar hypoplasia, Porokeratosis, Posterior column ataxia, Primary erythromelalgia, hyperoxaluria, Progressive familial intrahepatic cholestasis, Progressive pseudorheumatoid dysplasia, Propionic acidemia, Pseudohermaphroditism, Pseudohypoaldosteronism, Pseudoxanthoma elasticum-like disorder, Purine-nucleoside phosphorylase deficiency, Pyridoxal 5-phosphate-dependent epilepsy, Renal dysplasia, retinal pigmentary dystrophy, cerebellar ataxia, skeletal dysplasia, Reticular dysgenesis, Retinitis pigmentosa, Usher syndrome, Retinoblastoma, Retinopathy, RRM2B-related mitochondrial disease, Rubinstein-Taybi syndrome, Schnyder crystalline corneal dystrophy, Sebaceous tumor, Severe congenital neutropenia, Severe myoclonic epilepsy in infancy, Severe X-linked myotubular myopathy, onychodysplasia, facial dysmorphism, hypotrichosis, Short-rib thoracic dysplasia, Sialic acid storage disease, Sialidosis, Sideroblastic anemia, Small fiber neuropathy, Smith-Magenis syndrome, Sorsby fundus dystrophy, Spastic ataxia, Spastic paraplegia, Spermatogenic failure, Spherocytosis, Sphingomyelin/cholesterol lipidosis, Spinocerebellar ataxia, Split-hand/foot malformation, Spondyloepimetaphyseal dysplasia, Platyspondylic lethal skeletal dysplasia, Squamous cell carcinoma of the head and neck, Stargardt disease, Sucrase-isomaltase deficiency, Sudden infant death syndrome, Supravalvar aortic stenosis, Surfactant metabolism dysfunction, Tangier disease, Tatton-Brown-rahman syndrome, Thoracic aortic aneurysms and aortic dissections, Thrombophilia, Thyroid hormone resistance, TNF receptor-associated periodic fever syndrome (TRAPS), Tooth agenesis, Torsades de pointes, Transposition of great arteries, Treacher Collins syndrome, Tuberous sclerosis syndrome, Tyrosinase-negative oculocutaneous albinism, Tyrosinase-positive oculocutaneous albinism, Tyrosinemia, UDPglucose-4-epimerase deficiency, Ullrich congenital muscular dystrophy, Bethlem myopathy Usher syndrome, UV-sensitive syndrome, Van der Woude syndrome, popliteal pterygium syndrome, Very long chain acyl-CoA dehydrogenase deficiency, Vesicoureteral reflux, Vitreoretinochoroidopathy, Von Hippel-Lindau syndrome, von Willebrand disease, Waardenburg syndrome, Warsaw breakage syndrome, WFS1-Related Disorders, Wilson disease, Xeroderma pigmentosum, X-linked agammaglobulinemia, X-linked hereditary motor and sensory neuropathy, X-linked severe combined immunodeficiency, and Zellweger syndrome.


The development of nucleobase editing advances both the scope and effectiveness of genome editing. The nucleobase editors described here offer researchers a choice of editing with virtually no indel formation (NBE2), or more efficient editing with a low frequency (here, typically ≥1%) of indel formation (NBE3). That the product of base editing is, by definition, no longer a substrate likely contributes to editing efficiency by preventing subsequent product transformation, which can hamper traditional Cas9 applications. By removing the reliance on double-stranded DNA cleavage and stochastic DNA repair processes that vary greatly by cell state and cell type, nucleobase editing has the potential to expand the type of genome modifications that can be cleanly installed, the efficiency of these modifications, and the type of cells that are amenable to editing. It is likely that recent engineered Cas9 variants69, 70, 82 or delivery methods71 with improved DNA specificity, as well as Cas9 variants with altered PAM specificities,72 can be integrated into this strategy to provide additional nucleobase editors with improved DNA specificity or that can target an even wider range of disease-associated mutations. These findings also suggest that engineering additional fusions of dCas9 with enzymes that catalyze additional nucleobase transformations will increase the fraction of the possible DNA base changes that can be made through nucleobase editing. These results also suggest architectures for the fusion of other DNA-modifying enzymes, including methylases and demathylases, that mau enable additional types of programmable genome and epigenome base editing.


Materials and Methods

Cloning. DNA sequences of all constructs and primers used in this paper are listed in the Supplementary Sequences. Plasmids containing genes encoding NBE1, NBE2, and NBE3 will be available from Addgene. PCR was performed using VeraSeq ULtra DNA polymerase (Enzymatics), or Q5 Hot Start High-Fidelity DNA Polymerase (New England Biolabs). NBE plasmids were constructed using USER cloning (New England Biolabs). Deaminase genes were synthesized as gBlocks Gene Fragments (Integrated DNA Technologies), and Cas9 genes were obtained from previously reported plasmids.18 Deaminase and fusion genes were cloned into pCMV (mammalian codon-optimized) or pET28b (E. coli codon-optimized) backbones. sgRNA expression plasmids were constructed using site-directed mutagenesis. Briefly, the primers listed in the Supplementary Sequences were 5′ phosphorylated using T4 Polynucleotide Kinase (New England Biolabs) according to the manufacturer's instructions. Next, PCR was performed using Q5 Hot Start High-Fidelity Polymerase (New England Biolabs) with the phosphorylated primers and the plasmid pFYF1320 (EGFP sgRNA expression plasmid) as a template according to the manufacturer's instructions. PCR products were incubated with DpnI (20 U, New England Biolabs) at 37° C. for 1 h, purified on a QIAprep spin column (Qiagen), and ligated using QuickLigase (New England Biolabs) according to the manufacturer's instructions. DNA vector amplification was carried out using Mach1 competent cells (ThermoFisher Scientific).


In vitro deaminase assay on ssDNA. Sequences of all ssDNA substrates are listed in the Supplementary Sequences. All Cy3-labelled substrates were obtained from Integrated DNA Technologies (IDT). Deaminases were expressed in vitro using the TNT T7 Quick Coupled Transcription/Translation Kit (Promega) according to the manufacturer's instructions using 1 μg of plasmid. Following protein expression, 5 μL of lysate was combined with 35 μL of ssDNA (1.8 μM) and USER enzyme (1 unit) in CutSmart buffer (New England Biolabs) (50 mM potassium acetate, 29 mM Trisacetate, 10 mM magnesium acetate, 100 ug/mL BSA, pH 7.9) and incubated at 37° C. for 2 h. Cleaved U-containing substrates were resolved from full-length unmodified substrates on a 10% TBE-urea gel (Bio-Rad).


Expression and purification of His6-rAPOBEC1-linker-dCas9 fusions. E. Coli BL21 STAR (DE3)-competent cells (ThermoFisher Scientific) were transformed with plasmids encoding pET28b-His6-rAPOBEC-linker-dCas9 with GGS, (GGS)3, (SEQ ID NO: 596) XTEN, or (GGS)7 (SEQ ID NO: 597) linkers. The resulting expression strains were grown overnight in Luria-Bertani (LB) broth containing 100 μg/mL of kanamycin at 37° C. The cells were diluted 1:100 into the same growth medium and grown at 37° C. to OD600=˜0.6. The culture was cooled to 4° C. over a period of 2 h, and isopropyl-β-D-1-thiogalactopyranoside (IPTG) was added at 0.5 mM to induce protein expression. After ˜16 h, the cells were collected by centrifugation at 4,000 g and resuspended in lysis buffer (50 mM tris(hydroxymethyl)-aminomethane (Tris)-HCl, pH 7.0, 1 M NaCl, 20% glycerol, 10 mM tris(2-carboxyethyl)phosphine (TCEP, Soltec Ventures)). The cells were lysed by sonication (20 s pulse-on, 20 s pulse-off for 8 min total at 6 W output) and the lysate supernatant was isolated following centrifugation at 25,000 g for 15 min. The lysate was incubated with His-Pur nickel-nitriloacetic acid (nickel-NTA) resin (ThermoFisher Scientific) at 4° C. for 1 h to capture the His-tagged fusion protein. The resin was transferred to a column and washed with 40 mL of lysis buffer. The His-tagged fusion protein was eluted in lysis buffer supplemented with 285 mM imidazole, and concentrated by ultrafiltration (Amicon-Millipore, 100-kDa molecular weight cut-off) to 1 mL total volume. The protein was diluted to 20 mL in low-salt purification buffer containing 50 mM tris(hydroxymethyl)-aminomethane (Tris)-HCl, pH 7.0, 0.1 M NaCl, 20% glycerol, 10 mM TCEP and loaded onto SP Sepharose Fast Flow resin (GE Life Sciences). The resin was washed with 40 mL of this low-salt buffer, and the protein eluted with 5 mL of activity buffer containing 50 mM tris(hydroxymethyl)-aminomethane (Tris)-HCl, pH 7.0, 0.5 M NaCl, 20% glycerol, 10 mM TCEP. The eluted proteins were quantified on a SDSPAGE gel.


In vitro transcription of sgRNAs. Linear DNA fragments containing the T7 promoter followed by the 20-bp sgRNA target sequence were transcribed in vitro using the primers listed in the Supplementary Sequences with the TranscriptAid T7 High Yield Transcription Kit (ThermoFisher Scientific) according to the manufacturer's instructions. sgRNA products were purified using the MEGAclear Kit (ThermoFisher Scientific) according to the manufacturer's instructions and quantified by UV absorbance.


Preparation of Cy3-conjugated dsDNA substrates. Sequences of 80-nucleotide unlabeled strands are listed in the Supplementary Sequences and were ordered as PAGE-purified oligonucleotides from IDT. The 25-nt Cy3-labeled primer listed in the Supplementary Sequences is complementary to the 3′ end of each 80-nt substrate. This primer was ordered as an HPLC-purified oligonucleotide from IDT. To generate the Cy3-labeled dsDNA substrates, the 80-nt strands (5 μL of a 100 μM solution) were combined with the Cy3-labeled primer (5 μL of a 100 μM solution) in NEBuffer 2 (38.25 μL of a 50 mM NaCl, 10 mMTris-HCl, 10 mM MgCl2, 1 mM DTT, pH 7.9 solution, New England Biolabs) with dNTPs (0.75 μL of a 100 mM solution) and heated to 95° C. for 5 min, followed by a gradual cooling to 45° C. at a rate of 0.1° C./s. After this annealing period, Klenow exo (5 U, New England Biolabs) was added and the reaction was incubated at 37° C. for 1 h. The solution was diluted with Buffer PB (250 μL, Qiagen) and isopropanol (50 μL) and purified on a QIAprep spin column (Qiagen), eluting with 50 μL of Tris buffer.


Deaminase assay on dsDNA. The purified fusion protein (20 μL of 1.9 μM in activity buffer) was combined with 1 equivalent of appropriate sgRNA and incubated at ambient temperature for 5 min. The Cy3-labeled dsDNA substrate was added to final concentration of 125 nM and the resulting solution was incubated at 37° C. for 2 h. The dsDNA was separated from the fusion by the addition of Buffer PB (100 μL, Qiagen) and isopropanol (25 μL) and purified on a EconoSpin micro spin column (Epoch Life Science), eluting with 20 μL of CutSmart buffer (New England Biolabs). USER enzyme (1 U, New England Biolabs) was added to the purified, edited dsDNA and incubated at 37° C. for 1 h. The Cy3-labeled strand was fully denatured from its complement by combining 5 μL of the reaction solution with 15 μL of a DMSO-based loading buffer (5 mM Tris, 0.5 mM EDTA, 12.5% glycerol, 0.02% bromophenol blue, 0.02% xylene cyan, 80% DMSO). The full-length C-containing substrate was separated from any cleaved, U-containing edited substrates on a 10% TBE-urea gel (Bio-Rad) and imaged on a GE Amersham Typhoon imager.


Preparation of in vitro-edited dsDNA for high-throughput sequencing (HTS). The oligonucleotides listed in the Supplementary Sequences were obtained from IDT. Complementary sequences were combined (5 μL of a 100 μM solution) in Tris buffer and annealed by heating to 95° C. for 5 min, followed by a gradual cooling to 45° C. at a rate of 0.1° C./s to generate 60-bp dsDNA substrates. Purified fusion protein (20 μL of 1.9 μM in activity buffer) was combined with 1 equivalent of appropriate sgRNA and incubated at ambient temperature for 5 min. The 60-mer dsDNA substrate was added to final concentration of 125 nM and the resulting solution was incubated at 37° C. for 2 h. The dsDNA was separated from the fusion by the addition of Buffer PB (100 μL, Qiagen) and isopropanol (25 μL) and purified on a EconoSpin micro spin column (Epoch Life Science), eluting with 20 μL of Tris buffer. The resulting edited DNA (1 μL was used as a template) was amplified by PCR using the HTS primer pairs specified in the Supplementary Sequences and VeraSeq Ultra (Enzymatics) according to the manufacturer's instructions with 13 cycles of amplification. PCR reaction products were purified using RapidTips (Diffinity Genomics), and the purified DNA was amplified by PCR with primers containing sequencing adapters, purified, and sequenced on a MiSeq high-throughput DNA sequencer (Illumina) as previously described.73


Cell culture. HEK293T (ATCC CRL-3216), U2OS (ATCC-HTB-96) and ST486 cells (ATCC) were maintained in Dulbecco's Modified Eagle's Medium plus GlutaMax (ThermoFisher) supplemented with 10% (v/v) fetal bovine serum (FBS) and penicillin/streptomycin (1×, Amresco), at 37° C. with 5% CO2. HCC1954 cells (ATCC CRL-2338) were maintained in RPMI-1640 medium (ThermoFisher Scientific) supplemented as described above. Immortalized rat astrocytes containing the ApoE4 isoform of the APOE gene (Taconic Biosciences) were cultured in Dulbecco's Modified Eagle's Medium plus GlutaMax (ThermoFisher Scientific) supplemented with 10% (v/v) fetal bovine serum (FBS) and 200 μg/mL Geneticin (ThermoFisher Scientific).


Transfections. HEK293T cells were seeded on 48-well collagen-coated BioCoat plates (Corning) and transfected at approximately 85% confluency. Briefly, 750 ng of NBE and 250 ng of sgRNA expression plasmids were transfected using 1.5 μl of Lipofectamine 2000 (ThermoFisher Scientific) per well according to the manufacturer's protocol. Astrocytes, U2OS, HCC1954, HEK293T and ST486 cells were transfected using appropriate AMAXA NUCLEOFECTOR™ II programs according to manufacturer's instructions. 40 ng of infrared RFP (Addgene plasmid 45457)74 was added to the nucleofection solution to assess nucleofection efficiencies in these cell lines. For astrocytes, U2OS, and ST486 cells, nucleofection efficiencies were 25%, 74%, and 92%, respectively. For HCC1954 cells, nucleofection efficiency was <10%. Therefore, following trypsinization, the HCC1954 cells were filtered through a 40 micron strainer (Fisher Scientific), and the nucleofected HCC1954 cells were collected on a Beckman Coulter MoFlo XDP Cell Sorter using the iRFP signal (abs 643 nm, em 670 nm). The other cells were used without enrichment of nucleofected cells.


High-throughput DNA sequencing of genomic DNA samples. Transfected cells were harvested after 3 d and the genomic DNA was isolated using the Agencourt DNAdvance Genomic DNA Isolation Kit (Beckman Coulter) according to the manufacturer's instructions. On-target and off-target genomic regions of interest were amplified by PCR with flanking HTS primer pairs listed in the Supplementary Sequences. PCR amplification was carried out with Phusion high-fidelity DNA polymerase (ThermoFisher) according to the manufacturer's instructions using 5 ng of genomic DNA as a template. Cycle numbers were determined separately for each primer pair as to ensure the reaction was stopped in the linear range of amplification (30, 28, 28, 28, 32, and 32 cycles for EMX1, FANCF, HEK293 site 2, HEK293 site 3, HEK293 site 4, and RNF2 primers, respectively). PCR products were purified using RapidTips (Diffinity Genomics). Purified DNA was amplified by PCR with primers containing sequencing adaptors. The products were gel-purified and quantified using the QUANT-IT™ PicoGreen dsDNA Assay Kit (ThermoFisher) and KAPA Library Quantification Kit-Illumina (KAPA Biosystems). Samples were sequenced on an Illumina MiSeq as previously described.73


Data analysis. Sequencing reads were automatically demultiplexed using MiSeq Reporter (Illumina), and individual FASTQ files were analyzed with a custom Matlab script provided in the Supplementary Notes. Each read was pairwise aligned to the appropriate reference sequence using the Smith-Waterman algorithm. Base calls with a Q-score below 31 were replaced with N's and were thus excluded in calculating nucleotide frequencies. This treatment yields an expected MiSeq base-calling error rate of approximately 1 in 1,000. Aligned sequences in which the read and reference sequence contained no gaps were stored in an alignment table from which base frequencies could be tabulated for each locus.


Indel frequencies were quantified with a custom Matlab script shown in the Supplementary Notes using previously described criteria71. Sequencing reads were scanned for exact matches to two 10-bp sequences that flank both sides of a window in which indels might occur. If no exact matches were located, the read was excluded from analysis. If the length of this indel window exactly matched the reference sequence the read was classified as not containing an indel. If the indel window was two or more bases longer or shorter than the reference sequence, then the sequencing read was classified as an insertion or deletion, respectively.


All publications, patents, patent applications, publication, and database entries (e.g., sequence database entries) mentioned herein, e.g., in the Background, Summary, Detailed Description, Examples, and/or References sections, are hereby incorporated by reference in their entirety as if each individual publication, patent, patent application, publication, and database entry was specifically and individually incorporated herein by reference. In case of conflict, the present application, including any definitions herein, will control.


Supplementary Sequences


Primers used for generating sgRNA transfection plasmids. rev_sgRNA_plasmid was used in all cases. The pFYF1320 plasmid was used as template as noted in Materials and Methods section. SEQ ID NOs: 329-338 appear from top to bottom below, respectively.











rev_sgRNA_plasmid
GGTGTTTCGTCCTTTCCACAAG






fwd_p53_Y163C
GCTTGCAGATGGCCATGGCGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGC





fwd_p53_N239D
TGTCACACATGTAGTTGTAGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGC





fwd_AP0E4_C158R
GAAGCGCCTGGCAGTGTACCGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGC





fwd_EMX1
GAGTCCGAGCAGAAGAAGAAGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGC





fwd_FANCF
GGAATCCCTTCTGCAGCACCGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGC





fwd_HEK293_2
GAACACAAAGCATAGACTGCGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGC





fwd_HEK293_3
GGCCCAGACTGAGCACGTGAGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGC





fwd_HEK293_4
GGCACTGCGGCTGGAGGTGGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGC





fwd_RNF2
GTCATCTTAGTCATTACCTGGTTTTAGAGCTAGAAATAGCAAGTTAAAATAAGGC






Sequences of all ssDNA substrates used in in vitro deaminase assays. SEQ ID NOs: 339-341 appear from top to bottom below, respectively.











rAPOBEC1 substrate
Cy3-ATTATTATTATTCCGCGGATTTATTTATTTATTTATTTATTT






hAID/pmCDA1 substrate
Cy3-ATTATTATTATTAGCTATTTATTTATTTATTTATTTATTT





hAPOBEC3G substrate
Cy3-ATTATTATTATTCCCGGATTTATTTATTTATTTATTTATTT






Primers used for generating PCR products to serve as substrates for T7 transcription of sgRNAs for gel-based deaminase assay. rev_gRNA_T7 was used in all cases. The pFYF1320 plasmid was used as template as noted in Materials and Methods section. SEQ ID NOs: 342-365 appear from top to bottom below, respectively.











rev_sgRNA_T7
AAAAAAAGCACCGACTCGGTG






fwd_sgRNA_T7_dsDNA_2
TAATACGACTCACTATAGGCCGCGGATTTATTTATTTAAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_dsDNA_3
TAATACGACTCACTATAGGTCCGCGGATTTATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_dsDNA_4
TAATACGACTCACTATAGGTTCCGCGGATTTATTTATTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_dsDNA_5
TAATACGACTCACTATAGGATTCCGCGGATTTATTTATTGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_dsDNA_6
TAATACGACTCACTATAGGTATTCCGCGGATTTATTTATGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_dsDNA_7
TAATACGACTCACTATAGGTTATTCCGCGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_dsDNA_S
TAATACGACTCACTATAGGATTATTCCGCGGATTTATTTGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_dsDNA_9
TAATACGACTCACTATAGGTATTATTCCGCGGATTTATTGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_dsDNA_10
TAATACGACTCACTATAGGATTATTATCCGGGGATTTATGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_dsDNA_11
TAATACGACTCACTATAGGTATTATATTCCGCGGATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_dsDNA_12
TAATACGACTCACTATAGGTTATTATATTCCGCGGATTTGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_dsDNA_13
TAATACGACTCACTATAGGATTATTATATTCCGCGGATTGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_dsDNA_14
TAATACGACTCACTATAGGTATTATTATATTCCGCGGATGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_dsDNA_15
TAATACGACTCACTATAGGATTATTATTATTACCGCGGAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_dsDNA_18
TAATACGACTCACTATAGGATTATTATTATTATTACCGCGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_dsDNA_noC
TAATACGACTCACTATAGGATATTAATTTATTTATTTAAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_dsDNA_
TAATACGACTCACTATAGGGGAGGACGTGCGCGGCCGCCGTTTTAGAGCTAGAAATAGCA


APOE4_C112R






fwd_sgRNA_T7_dsDNA
TAATACGACTCACTATAGGGAAGCGCCTGGCAGTGTACCGTTTTAGAGCTAGAAATAGCA


APOE4_C158R






fwd_sgRNA_T7_dsDNA
TAATACGACTCACTATAGGCTGTGGCAGTGGCACCAGAAGTTTTAGAGCTAGAAATAGCA


CTNNB1_T41A






fwd_sgRNA_T7_dsDNA
TAATACGACTCACTATAGGCCTCCCGGCCGGCGGTATCCGTTTTAGAGCTAGAAATAGCA


HRAS_081R






fwd_sgRNA_T7_dsDNA
TAATACGACTCACTATAGGGCTTGCAGATGGCCATGGCGGTTTTAGAGCTAGAAATAGCA


53_Y163C






fwd_sgRNA_T7_dsDNA
TAATACGACTCACTATAGGACACATGCAGTTGTAGTGGAGTTTTAGAGCTAGAAATAGCA


53_Y236C






fwd_sgRNA_T7_dsDNA
TAATACGACTCACTATAGGTGTCACACATGTAGTTGTAGGTTTTAGAGCTAGAAATAGCA


53_N23SD







Sequences of 80-nucleotide unlabeled strands and Cy3-labeled universal primer used in gel-based dsDNA deaminase assays. SEQ ID NOs: 366-390 appear from top to bottom below, respectively.













Cy3-primer
Cy3-GTAGGTAGTTAGGATGAATGGAAGGTTGGTA








dsDNA_2
GTCCATGGATCCAGAGGTCATCCATTAAATAAATAAATCCGCGGGGCTATACCAACCTTCCATTCATCCTAACTACCTAC







dsDNA_3
GTCCATGGATCCAGAGGTCATCCATAAATAAATAAATCCGCGGAAGCTATACCAACCTTCCATTCATCCTAACTACCTAC







dsDNA_4
GTCCATGGATCCAGAGGTCATCCATAATAAATAAATCCGCGGAAGGCTATACCAACCTTCCATTCATCCTAACTACCTAC







dsSNA_5
GTCCATGGATCCAGAGGTCATCCAAATAAATAAATCGGCGGAATGGCTATACCAACCTTCCATTCATCCTAACTACCTAC







dsDNA_5
GTCCATGGATCCAGAGGTCATCCAATAAATAAATCCGCGGAATAGGCTATACCAACCTTCCATTCATCCTAACTACCTAG







dsDNA_7
GTCCATGGATCCAGAGGTCATCCATAAATAAATCCGCGGAATAAGGCTATACCAACCTTCCATTCATCCTAACTACCTAC







dsDNA_8
GTCCATGGATCCAGAGGTCATCCAAAATAAATCCGCGGAATAATGGCTATACCAACCTTCCATTCATCCTAACTACCTAC







dsDMA_3
GTCCATGGATCCAGAGGTCATCCAAATAAATCCGCGGAATAATAGGCTATACCAACCTTCCATTCATCCTAACTACCTAC







dsDMA_10
GTCCATGGATCCAGAGGTCATCCAATAAATCCGCGGATAATAATGGCTATACCAACCTTCCATTCATCCTAACTACCTAC







dsDNA_11
GTCCATGGATCCAGAGGTCATCCATAAATCCGCGGAATATAATAGGCTATACCAACCTTCCATTCATCCTAACTACCTAC







dsDNA_12
GTCCATGGATCCAGAGGTCATCCAAAATCCGCGGAATATAATAAGGCTATACCAACCTTCCATTCATCCTAACTACCTAC







dsDNA_13
GTCCATGGATCCAGAGGTCATCCAAATCCGCGGAATATAATAATGGCTATACCAACCTTCCATTCATCCTAACTACCTAC







dsDNA_14
GTCCATGGATCCAGAGGTCATCCAATCCGCGGAATATAATAATAGGCTATACCAACCTTCCATTCATCCTAACTACGTAC







dsDNA_15
GTCCATGGATCCAGAGGTCATCCAATCCGCGGTAATAATAATAAGGCTATACCAACCTTCCATTCATCCTAACTACGTAC







dsDNA_18
GTCCATGGATGCAGAGGTCATCCAGCGGTAATAATAATAATAATGGCTATACCAACCTTCCATTCATCCTAACTACCTAC







dsDNA_noC
GTCCATGGATCCAGAGGTCATCCATTAAATAAATAAATTAATATTACTATACCAACCTTCCATTCATCCTAACTACCTAC







dsDNA_8U
5Cy3-GTAGGTGTTAGGATGAATGGAAGGTTGGTAGATATTATCUGCGGATTTATTGGATGAGACCTCTGGATCCATGGACAT







dsDNA_APOE_
GCACCTCGCCGCGGTACTGCACCAGGCGGCCGCGCACGTCCTCCATGTCTACCAACCTTCCATTCATCCTAACTACCTAC



C112R








d5DNA_APOE_
CGGCGCCCTCGCGGGCCCCGGCCTGGTACACTGCCAGGCGCTTCTGCAGTAOCAACCTTCCATTCATCCTAACTACCTAC



C158R








dsDNA_CTNN5
GTCTTACCTGGACTCTGGAATCCATTCTGGTGCCACTGCCACAGCTCCTTACCAACCTTCCATTCATCCTAACTACCTAC



T41A








dsDNA_HRAS_
GGAGACGTGCCTGTTGGACATCCTGGATAOCGCCGGaCCGGGAGGAGTACTACCAACCTTCCATTCATCCTAACTACCTAC



Q61R








dsDNA_p53
ACCCCCGCCCGGCACCCGCGTCCGCGCCATGGCCATCTGCAAGCAGTCATACCAACCTTCCATTCATCCTAACTACCTAC



Y163C








dsDNA_p53_
AGGTTGGCTCTGACTGTACCACCATCCACTACAACTGCATGTGTAACAGTACCAACCTTCCATTCATCCTAACTACCTAC



Y236C








dsDNA_p53_
TGGCTCTGACTGTACCACCATCCACTACAACTACATGTGTGACAGTTCCTACCAACCTTCCATTCATCCTAACTACCTAC



N239D







Primers used for generating PCR products to serve as substrates for T7 transcription of sgRNAs for high-throughput sequencing. rev_gRNA_T7 (above) was used in all cases. The pFYF1320 plasmid was used as template as noted in Materials and Methods section. SEQ ID NOs: 391-442 appear from top to bottom below, respectively.











fwd_sgRNA_T7_HTS_base
TAATACGACTCACTATAGGTTATTTCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA






fwd_sgRNA_T7_HTS_1A
TAATACGACTCACTATAGGATATTTCGTGGATTTATTTA3TTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_1C
TAATACGACTCACTATAGGCTATTTCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_1G
TAATACGACTCACTATAGGGTATTTCGTGSATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_2A
TAATACGACTCACTATAGGTAATTTCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_2C
TAATACGACTCACTATAGGTCATTTCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_2G
TAATACGACTCACTATAGGTGATTTCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_3T
TAATACGACTCACTATAGGTTTTTTCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_3C
TAATACGACTCACTATAGGTTCTTTCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_3G
TAATACGACTCACTATAGGTTGTTTCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_4A
TAATACGACTCACTATAGGTTAATTCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_4C
TAATACGACTCACTATAGGTTACTTCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_4G
TAATACGACTCACTATAGGTTAGTTCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_5A
TAATACGACTCACTATAGGTTATATCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_5C
TAATACGACTCACTATAGGTTATCTCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_5G
TAATACGACTCACTATAGGTTATGTCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_6A
TAATACGACTCACTATAGGTTATTACGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_5C
TAATACGACTCACTATAGGTTATTCCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_6G
TAATACGACTCACTATAGGTTATTGCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_8A
TAATACGACTCACTATAGGTTATTTCATGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_8T
TAATACGACTCACTATAGGTTATTTCTTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_8C
TAATACGACTCACTATAGGTTATTTCCTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_9A
TAATACGACTCACTATAGGTTATTTCGAGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_9C
TAATACGACTCACTATAGGTTATTTCGCGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_9G
TAATACGACTCACTATAGGTTATTTCGGGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_10A
TAATACGACTCACTATAGGTTATTTCGTAGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_10T
TAATACGACTCACTATAGGTTATTTCGTIGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_10C
TAATACGACTCACTATAGGTTATTTCGTCGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_11A
TAATACGACTCACTATAGGTTATTTCGTGAATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_11T
TAATACGACTCACTATAGGTTATTTCGTGTATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_11C
TAATACGACTCACTATAGGTTATTTCGTGCATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_12T
TAATACGACTCACTATAGGTTATTTCGTGGTTTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_12C
TAATACGACTCACTATAGGTTATTTCGTGGCTTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_12G
TAATACGACTCACTATAGGTTATTTCGTGGGTTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_13A
TAATACGACTCACTATAGGTTATTTCGTGGAATTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_13C
TAATACGACTCACTATAGGTTATTTCGTGGACTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_13G
TAATACGACTCACTATAGGTTATTTCGTGGAGTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_77_HTS_multiC
TAATACGACTCACTATAGGTTCCCCCCCCGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_77_HTS_TCGCACCC_odd
TAATACGACTCACTATAGGCGCACCCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_77_HTS_CCTCGCAC_odd
TAATACGACTCACTATAGGCTCGCACGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_77_HTS_ACCCTCGC_odd
TAATACGACTCACTATAGGCCCTCGCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_77_HTS_GCACCCTC_even
TAATACGACTCACTATAGGCACCCTCGTGGATTTATTTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_TCGCACCC_even
TAATACGACTCACTATAGGTCGCACCCGTG3ATTTATTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_CCTCGCAC_even
TAATACGACTCACTATAGGCCTCGCACGTGGATTTATTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_ACCCTCGC_even
TAATACGACTCACTATAGGACCCTCGCGTG3ATTTATTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_GCACCCTC_even
TAATACGACTCACTATAGGGCACCCTCGTGGATTTATTAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_EMX1
TAATACGACTCACTATAGGGAGTCCGAGCAGAAGAAGAAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_FANCF
TAATACGACTCACTATAGGGGAATCCCTTCTGCAGCACCGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_HEK293_site2
TAATACGACTCACTATAGGGAACACAAAGCATAGACTGCGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_HEK293_site3
TAATACGACTCACTATAGGGGCCCAGACTGAGCACGTGAGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_HEK293_siie4
TAATACGACTCACTATAGGGGCACTGCGGCTGGAGGTGGGTTTTAGAGCTAGAAATAGCA





fwd_sgRNA_T7_HTS_RNF2
TAATACGACTCACTATAGGGTCATCTTAGTCATTACCTGGTTTTAGAGCTAGAAATAGCA






Sequences of in vitro-edited dsDNA for high-throughput sequencing (HTS). Shown are the sequences of edited strands. Reverse complements of all sequences shown were also obtained. dsDNA substrates were obtained by annealing complementary strands as described in Materials and Methods. Oligonucleotides representing the EMX1, FANCF, HEK293 site 2, HEK293 site 3, HEK293 site 4, and RNF2 loci were originally designed for use in the gel-based deaminase assay and therefore have the same 25-nt sequence on their 5′-ends (matching that of the Cy3-primer). SEQ ID NOs: 443-494 appear from top to bottom below, respectively.











Base sequence
ACGTAAACGGCCACAAGTTCTTATTTCGTGGATTTATTTATGGCATCTTCTTCAAGGACG






1A
ACGTAAACGGCCACAAGTTCATATTTCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





1C
ACGTAAACGGCCACAAGTTCCTATTTCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





1G
ACGTAAACGGCCACAAGTTCGTATTTCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





2A
ACGTAAACGGCCACAAGTTCTAATTTCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





2C
ACGTAAACGGCCACAAGTTCTCATTTCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





2G
ACGTAAACGGCCACAAGTTCTGATTTCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





3T
ACGTAAACGGCCACAAGTTCTTTTTTCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





3C
ACGTAAACGGCCACAAGTTCTTCTTTCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





3G
ACGTAAACGGCCACAAGTTCTTGTTTCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





4A
ACGTAAACGGCCACAAGTTCTTAATTCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





4C
ACGTAAACGGCCACAAGTTCTTACTTCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





4G
ACGTAAACGGCCACAAGTTCTTAGTTCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





5A
ACGTAAACGGCCACAAGTTCTTATATCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





5C
ACGTAAACGGCCACAAGTTCTTATCTCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





5G
ACGTAAACGGCCACAAGTTCTTATGTCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





5A
ACGTAAACGGCCACAAGTTCTTATTACGTGGATTTATTTATGGCATCTTCTTCAAGGACG





6C
ACGTAAACGGCCACAAGTTCTTATTCCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





5G
ACGTAAACGGCCACAAGTTCTTATTGCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





8A
ACGTAAACGGCCACAAGTTCTTATTTCATGGATTTATTTATGGCATCTTCTTCAAGGACG





8T
ACGTAAACGGCCACAAGTTCTTATTTCTTGGATTTATTTATGGCATCTTCTTCAAGGACG





8C
ACGTAAACGGCCACAAGTTCTTATTTCCTGGATTTATTTATGGCATCTTCTTCAAGGACG





9A
ACGTAAACGGCCACAAGTTCTTATTTCGAGGATTTATTTATGGCATCTTCTTCAAGGACG





9C
ACGTAAACGGCCACAAGTTCTTATTTCGCGGATTTATTTATGGCATCTTCTTCAAGGACG





9G
ACGTAAACGGCCACAAGTTCTTATTTCGGGGATTTATTTATGGCATCTTCTTCAAGGACG





10A
ACGTAAACGGCCACAAGTTCTTATTTCGTAGATTTATTTATGGCATCTTCTTCAAGGACG





10T
ACGTAAACGGCCACAAGTTCTTATTTCGTTGATTTATTTATGGCATCTTCTTCAAGGACG





10C
ACGTAAACGGCCACAAGTTCTTATTTCGTCGATTTATTTATGGCATCTTCTTCAAGGACG





11A
ACGTAAACGGCCACAAGTTCTTATTTCGTGAATTTATTTATGGCATCTTCTTCAAGGACG





11T
ACGTAAACGGCCACAAGTTCTTATTTCGTGTATTTATTTATGGCATCTTCTTCAAGGACG





11C
ACGTAAACGGCCACAAGTTCTTATTTCGTGCATTTATTTATGGCATCTTCTTCAAGGACG





12T
ACGTAAACGGCCACAAGTTCTTATTTCGTGGTTTTATTTATGGCATCTTCTTCAAGGACG





12C
ACGTAAACGGCCACAAGTTCTTATTTCGTGGCTTTATTTATGGCATCTTCTTCAAGGACG





12G
ACGTAAACGGCCACAAGTTCTTATTTCGTGGGTTTATTTATGGCATCTTCTTCAAGGACG





13A
ACGTAAACGGCCACAAGTTCTTATTTCGTGGAATTATTTATGGCATCTTCTTCAAGGACG





13C
ACGTAAACGGCCACAAGTTCTTATTTCGTGGACTTATTTATGGCATCTTCTTCAAGGACG





13G
ACGTAAACGGCCACAAGTTCTTATTTCGTGGAGTTATTTATGGCATCTTCTTCAAGGACG





multiC
ACGTAAACGGCCACAAGTTCTTCCCCCCCCGATTTATTTATGGCATCTTCTTCAAGGACG





TCGCACCC_odd
ACGTAAACGGCCACAAGTTTCGCACCCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





CCTCGCAC_odd
ACGTAAACGGCCACAAGTTCCTCGCACGTGGATTTATTTATGGCATCTTCTTCAAGGACG





ACCCTCGC_odd
ACGTAAACGGCCACAAGTTACCCTCGCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





GCACCCTC_odd
ACGTAAACGGCCACAAGTTGCACCCTCGTGGATTTATTTATGGCATCTTCTTCAAGGACG





TCGCACCC_even
ACGTAAACGGCCACAAGTATTCGCACCCGTGGATTTATTATGGCATCTTCTTCAAGGACG





CCTCGCAC_even
ACGTAAACGGCCACAAGTATCCTCGCACGTGGATTTATTATGGCATCTTCTTCAAGGACG





ACCCTCGC_even
ACGTAAACGGCCACAAGTATACCCTCGCGTGGATTTATTATGGCATCTTCTTCAAGGACG





GCACCCTC_even
ACGTAAACGGCCACAAGTATGCACCCTCGTGGATTTATTATGGCATCTTCTTCAAGGACG





EMX1_invitro
GTAGGTAGTTAGGATGAATGGAAGGTTGGTAGGCCTGAGTCCGAGCAGAAGAAGAAGGGCTCCCATCACATCAACCGGTG





FANCF_invitro
GTAGGTAGTTAGGATGAATGGAAGGTTGGTACTCATGGAATCCCTTCTGCAGCACCTGGATCGCTTTTCCGAGCTTCTGG





HEK293_site2_
GTAGGTAGTTAGGATGAATGGAAGGTTGGTAAACTGGAACACAAAGCATAGACTGCGGGGCGGGCCAGCCTGAATAGCTG


invitro






HEK293_site3_
GTAGGTAGTTAGGATGAATGGAAGGTTGGTACTTGGGGCCCAGACTGAGCACGTGATGGCAGAGGAAAGGAAGCCCTGCT


invitro






HEK293_site4_
GTAGGTAGTTAGGATGAATGGAAGGTTGGTACCGGTGGCACTGCGGCTGGAGGTGGGGGTTAAAGCGGAGACTCTGGTGC


invitro






RNF2_invitro
GTAGGTAGTTAGGATGAATGGAAGGTTGGTATGGCAGTCATCTTAGTCATTACCTGAGGTCGTTGTAACTCATATAA






Primers for HTS of in vitro edited dsDNA. SEQ ID NOs: 495-503 appear from top to bottom below, respectively.











fwd_invitro_HTS
ACACTCTTTCCCTACACGAGCTCTTCCGATCTNNNNACGTAAACGGCCACAA






rev_invitro_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTCGTCCTTGAAGAAGATGC





fwd_invitro_HEK_targets
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGTAGGTAGTTAGGATAATGGAA





rev_EMX1_invitro
TGGAGTTCAGACGTGTGCTCTTCCGATCTCACCGGTTGATGTGATGG





rev_FANCF_invitro
TGGAGTTCAGACGTGTGCTCTTCCGATCTCCAGAAGCTCGGAAAAGC





rev_HEK293_site2_invitro
TGGAGTTCAGACGTGTGCTCTTCCGATCTCAGCTATTCAGGCTGGC





rev_HEK293_site3_invitro
TGGAGTTCAGACGTGTGCTCTTCCGATCTAGCAGGGCTTCCTTTC





rev_HEK293_site4_invitro
TGGAGTTCAGACGTGTGCTCTTCCGATCTGCACCAGAGTCTCCG





rev_RNF2_invitro
TGGAGTTCAGACGTGTGCTCTTCCGATCTTTATATGAGTTACAACGAACACC






Primers for HTS of on-target and off-target sites from all mammalian cell culture experiments. SEQ ID NOs: 504-579 and 1869-1900 appear from top to bottom below, respectively.











fwd_EMX1_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNCAGCTCAGCCTGACTGTTGA






rev_EMX1_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTCTCGTGGGTTTGTGGTTGC





fwd_FANCF_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNCATTGCAGAGAGGCGTATCA





rev_FANCF_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGGGGTCCCAGGTGCTGAC





fwd_HEK293_site2_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNCCAGCCCCATCTGTCAAACT





rev_HEK293_site2_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTTGAATGGATTCCTTGGAAACAATGA





fwd_HEK293_Site3_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNATGTGGGCTGCCTAGAAAGG





rev_HEK293_sit93_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTCCCAGCCAAACTTGTCAACC





fwd_HEK293_site4_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGAACCCAGGTAGCCAGAGAC





rev_HEK293_site4_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTTCCTTTCAACCCGAACGGAG





fwd_RNF2_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNCTCTTCTTTATTTCCAGCAATGT





rev_RNF2_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGTTTTCATGTTCTAAAAATGTATCCCA





fwd_p53_Y163C_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNTACAGTACTCCCCTGCCCTC





rev_p53_Y163C_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGCTGCTCACCATCGCTATCT





fwd_p53_N239D_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNCCTCATCTTGGGCCTGTGTT





rev_p53_N239D_HTS 
TGGAGTTCAGACGTGTGCTCTTCCGATCTAAATCGGTAAGAGGTGGGCC





fwd_APOE4_C158R_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGCGGACATGGAGGACGTG





rev_APOE4_C158R_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTCTGTTCCACCAGGGGCCC





fwd_EMX1_off1_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNTGCCCAATCATTGATGCTTTT





rev_EMX1_off1_HTS 
TGGAGTTCAGACGTGTGCTCTTCCGATCTAGAAACATTTACCATAGACTATCACCT





fwd_EMX1_off2_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNAGTAGCCTCTTTCTCAATGTGC





rev_EWX1_off2_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGCTTTCACAAGGATGCAGTCT





fwd_EMX1_off3_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGAGCTAGACTCCGAGGGGA





rev_EMX1_off3_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTTCCTCGTCCTGCTCTCACTT





fwd_EMX1_off4_HTS
ACACTCTTTCCCTACACGACGCTCTTCC3ATCTNNNNAGAGGCTGAAGAGGAAGACCA





rev_EMX1_off4_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGGCCCAGCTGTGCATTCTAT





fwd_EMX1_off6_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNCCAAGAGGGCCAAGTCCTG





rev_EMX1_off6_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTCAGCGAGGAGTGACAGCC





fwd_EMX1_off7_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNCACTCCACCTGATCTCGGGG





rev_EMX1_off7_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTCGAGGAGGGAGGGAGCAG





fwd_EMX1_off8_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNACCACAAATGCCCAAGAGAC





rev_EMX1_off8_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGACACAGTCAAGGGCCGG





fwd_EMX1_off9_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNCCCACCTTTGAGGAGGCAAA





rev_EMX1_off9_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTTTCCATCTGAGAAGAGAGTGGT





fwd_EMX1_off10_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGTCATACCTTGGCCCTTCCT





rev_EMX1_off10_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTTCCCTAGGCCCACACCAG





fwd_FANCF_off1_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNAACCCACTGAAGAAGCAGGG





rev_FANCF_off1_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGGTGCTTAATCCGGCTCCAT





fwd_FANCF_off2_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNTCCAGTGTTTCCATCCCGAA





rev_FANCF_off2_HTS
TGGAGTTCAGACGTGTGOTCTTCCGATCTCCTCTGACCTCCACAACTCT





fwd_FANCF_off3_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNCTGGGTACAGTTCTGCGTGT





rev_FANCF_off3_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTTCACTCTGAGCATCGCCAAG





fwd_FANCF_off4_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGGTTTAGAGCCAGTGAACTAGAG





rev_FANCF_off4_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGCAAGACAAAATCCTCTTTATACTTTG





fwd_FANCF_off5_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGGGAGGGGACGGCCTTAC





rev_FANCF_off5_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGCCTCTGGCGAACATGGC





fwd_FANCF_off6_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNTCCTGGTTAAGAGCATGGGC





rev_FANCF_off6_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGATTGAGTCCCCACAGCACA





fwd_FANCF_off7_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNCCAGTGTTTCCCATCCCCAA





rev_FANCF_off7_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTTGACCTCCACAACTGGAAAAT





fwd_FANCF_off8_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGCTTCCAGACCCACCTGAAG





rev_FANCF_off8_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTACCGAGGAAAATTGCTTGTCG





fwd_HEK293_site2_off1_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGTGTGGAGAGTGAGTAAGCCA





rev_HEK293_site2_off1_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTACGGTAGGATGATTTCAGGCA





fwd_HEK293_site2_off2_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNCACAAAGCAGTGTAGCTCAGG





rev_HEK293_site2_off2_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTTTTTTGGTACTCGAGTGTTATTCAG





fwd_HEK293_site3_off1_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNTCCCCTGTTGACCTGGAGAA





rev_HEK293_site3_off1_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTCACTGTACTTGCCCTGACCA





fwd_HEK293_site3_off2_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNTTGGTGTTGACAGGGAGCAA





rev_HEK293_site3_off2_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTCTGAGATGTGGGCAGAAGGG





fwd_HEK293_site3_off3_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNTGAGAGGGAACAGAAGGGCT





rev_HEK293_site3_off3_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGTCCAAAGGCCCAAGAACCT





fwd_HEK2S3_site3_off4_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNTCCTAGCACTTTGGAAGGTCG





rev_HEK293_site3_off4_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGCTCATCTTAATCTGCTCAGCC





fwd_HEK293_site3_off5_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNAAAGGAGCAGCTCTTCCTGG





rev_HEK293_site3_off5_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGTCTGCACCATCTCCCACAA





fwd_HEK293_site4_off1_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGGCATGGCTTCTGAGACTCA





rev_HEK293_site4_off1_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGTCTCCCTTGCACTCCCTGTCTTT





fwd_HEK293_site4_off2_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNTTTGGCAATGGAGGCATTGG





rev_HEK293_site4_off2_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGAAGAGGCTGCCCATGAGAG





fwd_HEK293_site4_off3_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGGTCTGAGGCTCGAATCCTG





rev_HEK293_site4_off3_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTCTGTGGCCTCCATATCCCTG





fwd_HEK293_site4_off4_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNTTTCCACCAGAACTCAGCCC





rev_HEK293_site4_off4_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTCCTCGGTTCCTCCACAACAC





fwd_HEK293_site4_off5_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNCACGGGAAGGACAGGAGAAC





rev_HEK293_site4_off5_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGCAGGGGAGGGATAAAGCAG





fwd_HEK293_site4_off6_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNCCACGGGAGATGGCTTATGT





rev_HEK293_site4_off6_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTCACATCCTCACTGTGCCACT





fwd_HEK293_site4_off7_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGTCAGTCTCGGCCCCTCA





rev_HEK293_site4_off7_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGCCACTGTAAAGCTCTTGGG





fwd_HEK293_site4_off8_HTS
AGACTCTTTCCCTACAC3ACGCTCTTCCGATCTNNNNAGGGTAGAGGGACAGAGCTG





rev_HEX293_site4_off8_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGGACCCCACATAGTCAGTGC





fwd_HEK293_site4_off9_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGCTGTCAGCCCTATCTCCATC





rev_HEK293_site4_off9_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTTGGGCAATTAGGACAGGGAC





fwd_HEK293_site4_off10_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGCAGCGGAGGAGGTAGATTG





rev_HEK293_site4_off10_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTCTCAGTACCTGGAGTCCCGA





fwd_HEK2_ChIP_off1_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGACAGGCTCAGGAAAGCTGT





rev_HEK2_ChIP_off1_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTACACAAGCCTTTCTCCAGGG





fwd_HEK2_ChIP_off2_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNAATAGGGGGTGAGACTGGGG





rev_HEK2_ChIP_off2_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTGCCTCAGACGAGACTTGAGG





fwd_HEK2_ChIP_off3_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGGCCAGCAGGAAAGGAATCT





rev_HEK2_ChIp_off3_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTTGACTGCACCTGTAGCCATG





fwd_HEK2_ChIP_off4_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNTCAAGGAAATCACCCTGCCC





rev_HEK2_ChIP_off4_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTAACTTCCTTGGTGTGCAGCT





fwd_HEK2_ChIP_off5_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNATOGGCTCAGCTACGTCATG





rev_HEK2_ChIP_off5_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTAATAGCAGTGTGGT6GGCAA





fwd_HEK3_ChIP_off1_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNCGCACATCCCTTGTCTCTCT





rev_HEK3_ChIP_off1_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTCTACTGGAGCACACCCCAAG





fwd_HEK3_ChIP_off2_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNTGGGTCACGTAGCTTTGGTC





rev_HEK3_ChIP_off2_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTTGGTGGCCATGTGCAACTAA





fwd_HEK3_ChIP_off3_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNCTACTACGTGCCAGCTCAGG





rev_HEK3_ChIP_off3_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTACCTCCCCTCCTCACTAACC





fwd_HEK3_ChIP_off4_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGCCTCAGCTCCATTTCCTGT





rev_HEK3_ChIP_off4_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTAACCTTTATGGCACCAGGGG





fwd_HEK3_ChIP_off5_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGAGCTCAGCATTAGCAGGCT





rev_HEK3_ChIP_off5_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTTTCCTGGCTTTCCGATTCCC





fwd_HEK4_ChIp_off1_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNGTGCAATTGGAGGAGGAGCT





rev_HEK4_ChIp_off1_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTCACCAGCTACAGGCAGAACA





fwd_HEK4_ChIP_off3_HTS
ACACTCTTTCCCTACACGACGCTCTTCCGATCTNNNNCCTACCCCCAACACAGATGG





rev_HEK4_ChIP_off3_HTS
TGGAGTTCAGACGTGTGCTCTTCCGATCTCCACACAACTCAGGTCCTCC






Sequences of single-stranded oligonucleotide donor templates (ssODNs) used in HDR studies.









EMX1 sense


(SEQ ID NO: 580)


TCATCTGTGCCCCTCCCTCCCTGGCCCAGGTGAAGGTGTGGTTCCAGAAC





CGGAGGACAAAGTACAAACGGCAGAAGCTGGAGGAGGAAGGGCCTGAGTT





TGAGCAGAAGGAAGGGCTCCCATCACATCAACCGCGGTGGCGCATTGCCA





CGAAGCAGGCCAATGGGGAGGACATCGATGTCACCTCCAATGACTAGGGT





EMX1 antisense


(SEQ ID NO: 581)


ACCCTAGTCATTGGAGGTGACATCGATGTCCTCCCCATTGGCCTGCTTCG





TGGCAATGCGCCACCGGTTGATGTGATGGGAGCCCTTCTTCTTCTGCTCA





AACTCAGGCCCTTCCTCCTCCAGCTTCTGCCGTTTGTACTTTGTCCTCCG





GTTCTGGAACCACACCTTCACCTGGGCCAGGGAGGGAGGGGCACAGATGA





HEK293 site 3 sense


(SEQ ID NO: 582)


CATGCAATTAGTCTATTTCTGCTGCAAGTAAGGATGCATTTGTAGGCTTG





ATGCTTTTTTTCTGCTTCTCCAGCCCTGGCCTGGGTCAATCCTTGGGGCT





TAGACTGAGCACGTGATGGCAGAGGAAAGGAAGCCCTGCTTCCTCCAGAG





GGCGTCGCAGGACAGCTTTTCCTAGACAGGGGCTAGTATGTGCAGCTCCT





HEK293 site 3 antisense


(SEQ ID NO: 583)


AGGAGCTGCACATACTAGCCCCTGTCTAGGAAAAGCTGTCCTGCGACGCC





CTCTGGAGGAAGCAGGGCTTCCTTTCCTCTGCCATCACGTGCTCAGTCTA





AGCCCCAAGGATTGACCCAGGCCAGGGCTGGAGAAGCAGATAAAAAGCAT





CAAGCCTACAAATGCATGCTTACTTGCAGCAGAAATAGACTAATTGCATG





HEK site 4 sense


(SEQ ID NO: 584)


GGCTGACAAAGGCCGGGCTGGGTGGAAGGAAGGGAGGAAGGGCGAGGCAG





AGGGTCCAAAGCAGGATGACAGGCAGGGGCACCGCGGCGCCCCGGTGGCA





TTGCGGCTGGAGGTGGGGGTTAAAGCGGAGACTCTGGTGCTGTGTGACTA





CAGTGGGGGCCGTGCCCTCTCTGAGCCCCCGCCTCCAGGCCTGTGTGTGT





HEK site 4 antisense


(SEQ ID NO: 585)


ACACACACAGGCCTGGAGGCGGGGGCTCAGAGAGGGCAGGGCCOCCACTG





TAGTCACACAGCACCAGAGTCTCCGCTTTAACCCCCACCTCCAGCCGCAA





TGCCACCGGGGCGCCGCGGTGCCCCTGCCTGTCATCCTGCTTTGGACCCT





CTGCCTCGCCCTTCCTCCCTTCCTTCCACCCAGCCCGGCCTTTGTCAGCC





APOE4 sense


(SEQ ID NO: 743)


AGCACCGAGGAGCTGCGGGTGCGCCTCGCCTCCCACCTGCGCAAGCTGCG





TAAGCGGCTCCTCCGCGATGCCGATGACCTGCAGAAGTGCCTGGCAGTGT





ACCAGGCCGGGGCCCGCGAGGGCGCCGAGCGCGGCCTCAGCGCCATCCGC





GAGCGCCTGGGGCCCCTGGTGGAACAGGGCCGCGTGCGGGCCGCCACTGT





APOE4 antisense


(SEQ ID NO: 744)


ACAGTGGCGGCCCGCACGCGGCCCTGTTCCACCAGGGGCCCCAGGCGCTC





GCGGATGGCGCTGAGGCCGCGCTCGGCGCCCTCGCGGGCCCCGGCCTGGT





ACACTGCCAGGCACTTCTGCAGGTCATCGGCATCGCGGAGGAGCCGCTTA





CGCAGCTTGCGCAGGTGGGAGGCGAGGCGCACCCGCAGCTCCTCGGTGCT





p53 Y163C sense


(SEQ ID NO: 745)


ACTCCCCTGCCCTCAACAAGATGTTTTGCCAACTGGCCAAGACCTGCCCT





GTGCAGCTGTGGGTTGATTCCACACCCCCGCCCGGCACCCGCGTCCGCGC





CATGGCCATCTACAAGCAGTCACAGCACATGACGGAGGTTGTGAGGCGCT





GCCCCCACCATGAGCGCTGCTCAGATAGCGATGGTGAGCAGCTGGGGCTG





p53 Y163C antisense


(SEQ ID NO: 746)


CAGCCCCAGCTGCTCACCATCGCTATCTGAGCAGCGCTCATGGTGGGGGC





AGCGCCTCACAACCTCCGTCATGTGCTGTGACTGCTTGTAGATGGCCATG





GCGCGGACGCGGGTGCCGGGCGGGGGTGTGGAATCAACCCACAGCTGCAC





AGGGCAGGTCTTGGCCAGTTGGCAAAACATCTTGTTGAGGGCAGGGGAGT







Deaminase Gene gBlocks Gene Fragments









hAID


(SEQ ID NO: 586)


CATCCTTGGTACCGAGCTCGGATCCAGCCACCATGGATAGCCTCTTGATG





AATAGACGCAAGTTCCTGTATCAGTTTAAAAACGTGAGATGGGCAAAAGG





CCGACGAGAGACATATCTGTGCTATGTCGTTAAGCGCAGAGATTCAGCCA





CCAGTTTCTCTCTCGACTTCGGCTACCTGOGGAACAAGAATGGTTGCCAT





GTTGAGCTCCTGTTCCTGAGGTATATCAGCGACTGGGATTTGGACCCAGG





GCGGTGCTATAGGGTGACATGGTTTACCTCCTGGTCACCTTGTTATGACT





GCGCGCGGCATGTTGCCGATTTTCTGAGAGGGAACCCTAACCTGTCTCTG





AGGATCTTCACCGCGCGACTGTACTTCTGTGAGGACCGGAAAGCCGAACC





CGAGGGACTGAGACGCCTCCACAGAGCGGGTGTGCAGATTGCCATAATGA





CCTTTAAGGACTACTTCTACTGCTGGAACACCTTCGTCGAAAATCACGAG





CGGACTTTCAAGGCTTGGGAAGGATTGCATGAAAACAGCGTCAGGCTTTC





CAGGCAGCTTCGCCGCATTCTTCTCCCGTTGTACGAGGTTGATGACCTCA





GAGATGCCTTTAGAACACTGGGACTGTAGGCGGCCGCTCGATTGGTTTGG





TGTGGCTCTAA





rAPOBEC1 (mammalian)


(SEQ ID NO: 587)


CATCCTTGGTACCGAGCTCGGATCCAGCCACCATGAGCTCAGAGACTGGC





CCAGTGGCTGTGGACCCCACATTGAGACGGCGGATCGAGCCCCATGAGTT





TGAGGTATTCTTCGATCCGAGAGAGCTCCGCAAGGAGACCTGCCTGCTTT





ACGAAATTAATTGGGGGGGCCGGCACTCCATTTGGCGACATACATCACAG





AACACTAACAAGCACGTCGAAGTCAACTTCATCGAGAAGTTCACGACAGA





AAGATATTTCTGTCCGAACACAAGGTGCAGCATTACCTGGTTTCTCAGCT





GGAGCCCATGCGGCGAATGTAGTAGGGCCATCACTGAATTCCTGTCAAGG





TATCCCCACGTCACTCTGTTTATTTACATCGCAAGGCTGTACCACCACGC





TGACCCCCGCAATCGACAAGGCCTGCGGGATTTGATCTCTTCAGGTGTGA





CTATCCAAATTATGACTGAGCAGGAGTCAGGATACTGCTGGAGAAACTTT





GTGAATTATAGCCCGAGTAATGAAGCCCACTGGCCTAGGTATCCCCATCT





GTGGGTACGACTGTACGTTCTTGAACTGTACTGCATCATACTGGGCCTGC





CTCCTTGTCTCAACATTCTGAGAAGGAAGCAGCCACAGCTGACATTCTTT





ACCATCGCTCTTCAGTCTTGTCATTACCAGCGACTGCCCCCACACATTCT





CTGGGCCACCGGGTTGAAATGAGCGGCCGCTCGATTGGTTTGGTGTGGCT





CTAA





pmCDA1


(SEQ ID NO: 588)


CATCCTTGGTACCGAGCTCGGATCCAGCCACCATGACAGACGCTGAATAT





GTTAGGATCCATGAAAAACTGGATATCTATACATTTAAGAAGCAGTTCTT





CAATAACAAAAAGTCAGTATCTCACAGATGCTATGTCCTGTTCGAACTCA





AGAGAAGAGGAGAAAGGCGGGCCTGTTTCTGGGGGTACGCGGTTAATAAA





CCCCAGTCCGGGACCGAGAGGGGGATTCACGCCGAGATCTTTTCAATTAG





GAAGGTTGAAGAGTATCTTCGCGACAATCCCGGTCAGTTCACAATTAACT





GGTACAGCTCCTGGAGCCCTTGCGCTGATTGCGCCGAGAAAATACTCGAA





TGGTACAACCAGGAGTTGAGAGGCAATGGCCACACTCTCAAGATTTGGGC





TTGCAAGCTTTACTACGAGAAGAACGCGAGAAATCAGATTGGCTTGTGGA





ACCTCAGGGACAACGGGGTCGGGTTGAATGTTATGGTGTCCGAACATTAC





CAGTGCTGTAGAAAGATCTTCATTCAGTCCAGTCACAATCAGCTGAACGA





GAACAGATGGCTGGAGAAAACACTGAAACGGGCAGAGAAAAGGCGCTCAG





AGCTGAGTATCATGATCCAGGTCAAAATCTCTGCATACAACCAAAAGCCC





GGCTGTATAAGCGGCCGCTCGATTGGTTTGGTGTGGCTCTAA





haPOBEC3G


(SEQ ID NO: 589)


CATCCTTGGTACCGAGCTCGGATCCAGCCACCATGGAGCTGAAGTATCAC





CCTGAGATGCGGTTTTTCCACTGGTTTAGTAAGTGGCGCAAACTTCATCG





GGATCAGGAGTATGAAGTGACCTGGTATATCTCTTGGTCTCCCTGCACAA





AATGTACACGCGACATGGCCACATTTCTGGCCGAGGATCCAAAGGTGACG





CTCACAATCTTTGTGGCCCGCCTGTATTATTTCTGGGACCCGGATTATCA





GGAGGCACTTAGGTCATTGTGCCAAAAGCGCGACGGACCACGGGCGACTA





TGAAAATCATGAATTATGACGAATTCCAGCATTGCTGGAGTAAGTTTGTG





TACAGCCAGCGGGAGCTGTTCGAGCCCTGGAACAATCTTCCCAAGTACTA





CATACTGCTTCACATTATGTTGGGGGAGATCCTTCGGCACTCTATGGATC





CTCCTACCTTTACGTTTAACTTTAATAATGAGCCTTGGGTTCGCGGGCGC





CATGAAACCTATTTGTGCTACGAGGTCGAGCGGATGCATAATGATACGTG





GGTCCTGCTGAATCAGAGGAGGGGGTTTCTGTGTAACCAGGCTCCACATA





AACATGGATTTCTCGAGGGGCGGCACGCCGAACTGTGTTTCCTTGATGTG





ATACCTTTCTGGAAGCTCGACCTTGATCAAGATTACAGGGTGACGTGTTT





CACCTCCTGGTCACCCTGCTTCAGTTGCGCCCAAGAGATGGCTAATTTAT





CAGTAAGAACAAGCATGTGTCCCTCTGTATTTTTACAGCCAGAATTTATG





ATGACCAGGGCCGGTGCCAGGAGGGGCTGCGGACACTCGCTGAGGCGGGC





GCGAAGATCAGCATAATGACATACTCCGAATTCAAACACTGTTGGGACAC





TTTTGTGGACCACCAGGGCTGCCCATTTCAGCCGTGGGATGGGCTCGACG





AACATAGTCAGGATCTCTCAGGCCGGCTGOGAGCCATATTGCAGAACCAG





GAGAATTAGGCGGCCGCTCGATTGGTTTGGTGTGGCTCTAA





rAPOBEC1 (E. Coli)


(SEQ ID NO: 590)


GGCCGGGGATTCTAGAAATAATTTTGTTTAACTTTAAGAAGGAGATATAC





CATGGATGTCTTCTGAAACCGGTCCGGTTGCGGTTGACCCGACCCTGCGT





CGTCGTATCGAACCGCACGAATTCGAAGTTTTCTTCGACCCGCGTGAACT





GCGTAAAGAAACCTGCCTGCTGTACGAAATCAACTGGGGTGGTCGTCACT





CTATCTGGCGTCACACCTCTCAGAACACCAACAAACACGTTGAAGTTAAC





TTCATCGAAAAATTCACCACCGAACGTTACTTCTGCCCGAACACCCGTTG





CTCTATCACCTGGTTCCTGTCTTGGTCTCCGTGCGGTGAATGCTCTCGTG





CGATCACCGAATTCCTGTCTCGTTACCCGCACGTTACCCTGTTCATCTAC





ATCGCGCGTCTGTACCACCACGCGGACCCGCGTAACCGTCAGGGTCTGCG





TGACCTGATCTCTTCTGGTGTTACCATCCAGATCATGACCGAACAGGAAT





CTGGTTACTGCTGGCGTAACTTCGTTAACTACTCTCCGTCTAACGAAGCT





GCACTGGCCGCGTTACTCCGCACCTGTGGGTTCGTCTGTACGTTCTGGAA





CTGTACTGCATCATCCTGGGTCTGCCGCCGTGCCTGAACATCCTGCGTCG





TAAACAGCCGCAGCTGACCTTCTTCACCATCGCGCTGCAGTCTTGCCACT





ACCAGCGTCTGCCGCCGCACATCCTGTGGGCGACCGGTCTGAAAGGTGGT





AGTGGAGGGAGCGGCGGTTCAATGGATAAGAAATAC







Amino Acid Sequences of NBE1, NBE2, and NBE3.










NBE1 for E. Coli expression (His6-rAPOBEC1-XTEN-dCas9)



(SEQ ID NO: 591)



MGSSHHHHHHMSSETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSIWRHTSQNTN






KHVEVNFIEKFTTERYFCPNTRCSITWFLSWSPCGECSRAITEFLSRYPHVTLFIYIARLYHHADPRNRQGL





RDLISSGVTIQIMTEQESGYCWRNFVNYSPSNEAHWPRYPHLWVRLYVLELYCIILGLPPCLNILRRKQPQ





LTFFTIALQSCHYQRLPPHILWATGLKSGSETPGTSESATPESDKKYSIGLAIGTNSVGWAVITDEYKVPSK





KFKVLGNTDRHSIKKNLIGALLFDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRL





EESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDL





NPDNSDVDKLFIQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSL





GLTPNFKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSA





SMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGTEELL





VKLNREDLLRKQRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRF





AWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVTE





GMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKIIKDK





DFLDNEENEDILEDIVLTLTLFEDREMEERLKTYAHLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQS





GKTILDFLKSDGFANRNFMQLIHDDSLTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDEL





VKVMGRHKPENIVIEMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQ





NGRDMYVDQELDINRLSDYDVDAIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQL





LNAKLITQRKFDNLTKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLK





SKLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAKSEQEIG





KATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLSMPQVNIVKKTEVQT





GGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSS





FEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKL





KGSPEDNEQKQLFVEQHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTINL





GAPAAFKYFDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGDSGGSPKKKRKV





NBE1 for Mammalian expression (rAPOBEC1-XTEN-dCas9-NLS)


(SEQ ID NO: 592)



MSSETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSIWRHTSQNTNKHVEVNFIEKF






TTERYFCPNTRCSITWFLSWSPCGECSRAITEFLSRYPHVTLFIYIARLYHHADPRNRQGLRDLISSGVTIQ





IMTEQESGYCWRNFVNYSPSNEAHWPRYPHLWVRLYVLELYCIILGLPPCLNILRRKQPQLTFFTIALQSC





HYQRLPPHILWATGLKSGSETPGTSESATPESDKKYSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDR





HSIKKNLIGALLFDSGETAEATRLKRTARRRYTRRKNRICYLIQEIFSNEMAKVDDSFFHRLEESFLVEEDKK





HERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLF





IQLVQTYNQLFEENPINASGVDAKAISARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNFDL





AEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQ





DLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQ





RTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFAWMTRKSEETITP





WNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNNELTKVKYVTEGMRKPAFLSGEQ





KKAIVDLLFKTNRKVTVKQLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKHKDKDFLDNEENEDILE





DIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFA





NRNFIAGLIHDDSLTFKEDIQKAQVSGQGDSLHEHIANLAGSPAKKGILQPVKVVDELVKVMGRHKPENIVI





EMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDI





NRLSDYDVDAIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNL





TKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKDFQF





YKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRMIAKSEQEIGKATAKYFFYSNIM





NFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLSMPQNIVKKTEVQTGGFSKESILPKRN





SDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKG





YKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQL





FVEQHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTI





DRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGDSGGSPKKKRKV














Alternative NBE1 for Mammalian expression with human APOBEC1 (hAPOBEC1-



XTEN-dCas9-NLS)


(SEQ ID NO: 5737)



MTSEKGPSTGDPTLRRRIEPWEFDVFYDPRELRKEACLLYEIKWGMSRKIWRSSGKNTTN






HVEVNFIKKFTSERDFHPSMSCSITWFLSWSPCWECSQAIREFLSRHPGVTLVIYVARLFW





HMDQQNRQGLRDLVNSGVTIQIMRASEYYHCWRNFVNYPPGDEAHWPQYPPLWMMLY





ALELHCIILSLPPCLKISRRWQNHLTFFRLHLQNCHYQTIPPHILLATGLIHPSVAWRGSETP





GTSESATPESDKKYSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALL





FDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKK





HERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGD





LNPDNSDVDKLFIQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKK





NGLFGNLIALSLGLTPNFKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAA





KNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQ





SKNGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRTFDNGSIPHQIH





LGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFAWMTRKSEETITPW





NFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVTEGMR





KPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFDSVETSGVEDRFNASLGTYH





DLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRY





TGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKEDIQKAQVSGQ





GDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMARENQTTQKGQK





NSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINRLSD





YDVDAIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQ





RKFDNLTKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVK





VITLKSKLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDY





KVYDVRKMIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETNGETGEIVW





DKGRDFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKDWDPKKYGG





FDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKD





LIIKLPKYSLFELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNE





QKQLFVEQHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTL





TNLGAPAAFKYFDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGDSGGSPKKK





RKV





NBE2 (rAPOBEC1-XTEN-dCas9-UGI-NLS)


(SEQ ID NO: 593)



MSSETGPVAVDPTLRRRIEPHEFEVFFDFRELRKETCLLYEINWGGRHSIWRHTSQNTNKHVEVNFIEKF






TTERYFCPNTRCSITWFLSWSPCGECSRAITEFLSRYPHVTLFIYIARLYHHADPRNRQGLRDLISSGVTIQ





IMTEQESGYCWRNFVNYSPSNEAHWPRYPHLWVRLYVLELYCIILGLPPCLNILRRKQPQLTFFTIALQSC





HYQRLPPHILWATGLKSGSETPGTSESATPESDKKYSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDR





HSIKKNLIGALLFDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKK





HERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLF





IQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNFDL





AEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQ





DLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQ





RTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFAWMTRKSEETITP





WNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQ





KKAIVDLLFKTNRKVTVKQLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILE





DIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFA





NRNFMQLIHDDSLTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVI





EMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDI





NRLSDYDVDAIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNL





TKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKDFQF





YKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAKSEQEIGKATAKYFFYSNIM





NFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRN





SDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKG





YKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQL





FVEQHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTI





DRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGDSGGSTNLSDIIEKETGKQLVIQESILMLPEEVEEVIG





NKPESDILVHTAYDESTDENVMLLTSDAPEYKPWALVIQDSNGENKIKMLSGGSPKKKRKV





NBE3 (rAPOBEC1-XTEN-Cas9n-UGI-NLS)


(SEQ ID NO: 594)



MSSETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSIWRHTSQNTNKHVEVNFIEKF






TTERYFCPNTRCSITWFLSWSPCGECSRAITEFLSRYPHVTLFIYIARLYHHADPRNRQGLRDLISSGVTIQ





IMTEQESGYCWRNFVNYSPSNEAHWPRYPHLWVRLYVLELYCIILGLPPCLNILRRKQPQLTFFTIALQSC





HYQRLPPHILWATGLKSGSETPGTSESATPESDKKYSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDR





HSIKKNLIGALLFDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKK





HERHPIFGNIVDEVAYHEKYFTIYHLRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLF





IQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNFDL





AEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQ





DLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQ





RTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPVYVGPLARGNSRFAWMTRKSEETITP





WNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQ





KKAIVDLLFKTNRKVTVKQLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILE





DIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFA





NRNFMQLIHDDSLTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVI





EMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDI





NRLSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNL





TKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKDFQF





YKVREINNYHHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAKSEQEIGKATAKYFFYSNIM





NFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRN





SDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAKG





YKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQL





FVEQHKHYLDENIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTI





DRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGDSGGSTNLSDIIEKETGKQLVIQESILMLPEEVEEVIG





NKPESDILVHTAYDESTDENVMLLTSDAPEYKPWALVQDSNGENKIKMLSGGSPKKKRKV





pmCDA1-XTEN-dCas9-UGI (bacteria)


(SEQ ID NO: 5742)



MTDAEYVRIHEKLDIYTFKKQFFNNKKSVSHRCYVLFELKRRGERRACFWGYAVNKPQS






GTERGIHAEIFSIRKVEEYLRDNPGQFTINWYSSWSPCADCAEKILEWYNQELRGNGHTL





KIWACKLYYEKNARNQIGLWNLRDNGVGLNVMVSEHYQCCRKIFIQSSHNQLNENRWL





EKTLKRAEKRRSELSIMIQVKILHTTKSPAVSGSETPGTSESATPESDKKYSIGLAIGTNSV





GWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAEATRLKRTARRRYTRRK





NRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYH





LRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFE





ENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNFDLA





EDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSAS





MIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILE





KMDGTEELLVKLNREDLLRKQRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEK





ILTFRIPYYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLP





NEKVLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVK





QLKEDYFKKIECFDSVETSGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLT





LFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLK





SDGFANRNFMQLIHDDSLTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVV





DELVKVMGRHKPENIVIEMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENT





QLQNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDAIVPQSFLKDDSIDNKVLTRSDKN





RGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERGGLSELDKAGFIKRQL





VETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKDFQFYKVREINNY





HHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAKSEQEIGKATAKYFFYS





NIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLSMPQVNIVKKTEVQ





TGGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSV





KELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQ





KGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISEFSKRVIL





ADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEV





LDATLIHQSITGLYETRIDLSQLGGDSGGSMTNLSDIIEKETGKQLVIQESILMLPEEVEEVI





GNKPESDILVHTAYDESTDENVMLLTSDAPEYKPWALVIQDSNGENKIKML





pmCDA1-XTEN-nCas9-UGI-NLS (mammalian construct)


(SEQ ID NO: 5743)



MTDAEYVRIHEKLDIYTFKKQFFNNKKSVSHRCYVLFELKRRGERRACFWGYAVNKPQS






GTERGIHAEIFSIRKVEEYLRDNPGQFTINWYSSWSPCADCAEKILEWYNQELRGNGHTL





KIWACKLYYEKNARNQIGLWNLRDNGVGLNVMVSEHYQCCRKIFIQSSHNQLNENRWL





EKTLKRAEKRRSELSIMIQVKILHTTKSPAVSGSETPGTSESATPESDKKYSIGLAIGTNSV





GWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETAEATRLKRTARRRYTRRK





NRICYLQEIFSNEMAKVDDSFFHRLEESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYH





LRKKLVDSTDKADLRLIYLALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFE





ENPINASGVDAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNFDLA





EDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSAS





MIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILE





KMDGTEELLVKLNREDLLRKQRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEK





ILTFRIPYYVGPLARGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLP





NEKVLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVK





QLKEDYFKKIECFDSVETSGVEDRFNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLT





LFEDREMIEERLKTYAHLFDDKVMKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLK





SDGFANRNFMQLIHDDSLTFKEDIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVV





DELVKVMGRHKPENIVIEMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENT





QLQNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDHIVPQSFLKDDSIDNKVLTRSDKN





RGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERGGLSELDKAGFIKRQL





VETRQITKHVAQILDSRMNTKYDENDKLIREVKVITLKSKLVSDFRKDFQFYKVREINNY





HHAHDAYLNAVVGTALIKKYPKLESEFVYGDYKVYDVRKMIAKSEQEIGKATAKYFFYS





NIMNFFKTEITLANGEIRKRPLIETNGETGEIVWDKGRDFATVRKVLSMPQVNIVKKTEVQ





TGGFSKESILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSV





KELLGITIMERS SFEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQ





KGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEIIEQISEFSKRVIL





ADANLDKVLSAYNKHRDKPIREQAENIIHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEV





LDATLIHQSITGLYETRIDLSQLGGDSGGSTNLSDIIEKETGKQLVIQESILMLPEEVEEVIG





NKPESDILVHTAYDESTDENVMLLTSDAPEYKPWALVIQDSNGENKIKMLSGGSPKKKR





KV





huAPOBEC3G-XTEN-dCas9-UGI (bacteria)


(SEQ ID NO: 5744)



MDPPTFTFNFNNEPWVRGRHETYLCYEVERMHNDTWVLLNQRRGFLCNQAPHKHGFLE






GRHAELCFLDVIPFWKLDLDDYRVTCFTSWSPCFSCAQEMAKFISKNKHVSLCIFTARIY





DDQGRCQEGLRTLAEAGAKISIMTYSEFKHCWDTFVDHQGCPFQPWDGLDEHSQDLSGR





LRAILQSGSETPGTSESATPESDKKYSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDR





HSIKKNLIGALLFDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRL





EESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMI





KFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLE





NLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIG





DQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQL





PEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRT





FDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFAWMT





RKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTK





VKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFDSVETSGVEDR





FNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKV





MKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKED





IQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMAREN





QTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQ





ELDINRLSDYDVDAIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQ





LLNAKLITQRKFDNLTKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDE





NDKLIREVKVITLKSKLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLE





SEFVYGDYKVYDVRKMIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETN





GETGEIVWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKD





WDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAK





GYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKL





KGSPEDNEQKQLFVEQHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQA





ENIIHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD





SGGSMTNLSDIIEKETGKQLVIQESILMLPEEVEEVIGNKPESDILVHTAYDESTDENVMLL





TSDAPEYKPWALVIQDSNGENKIKML





huAPOBEC3G-XTEN-nCas9-UGI-NLS (mammalian construct)


(SEQ ID NO: 5745)



MDPPTFTFNFNNEPWVRGRHETYLCYEVERMHNDTWVLLNQRRGFLCNQAPHKHGFLE






GRHAELCFLDVIPFWKLDLDQDYRVTCFTSWSPCFSCAQEMAKFISKNKHVSLCIFTARIY





DDQGRCQEGLRTLAEAGAKISIMTYSEFKHCWDTFVDHQGCPFQPWDGLDEHSQDLSGR





LRAILQSGSETPGTSESATPESDKKYSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDR





HSIKKNLIGALLFDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRL





EESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMI





KFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLE





NLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIG





DQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQL





PEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRT





FDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFAWMT





RKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTK





VKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFDSVETSGVEDR





FNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKV





MKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKED





IQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMAREN





QTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQ





ELDINRLSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQ





LLNAKLITQRKFDNLTKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDE





NDKLIREVKVITLKSKLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLE





SEFVYGDYKVYDVRKMIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETN





GETGEIVWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKD





WDPKKYGGFDSPTVAYS VLVVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAK





GYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKL





KGSPEDNEQKQLFVEQHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQA





ENIIHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD





SGGSTNLSDIIEKETGKQLVIQESILMLPEEVEEVIGNKPESDILVHTAYDESTDENVMLLT





SDAPEYKPWALVIQDSNGENKIKMLSGGSPKKKRKV





huAPOBEC3G (D316R_D317R)-XTEN-nCas9-UGI-NLS (mammalian construct)


(SEQ ID NO: 5746)



MDPPTFTFNFNNEPWVRGRHETYLCYEVERMHNDTWVLLNQRRGFLCNQAPHKHGFLE






GRHAELCFLDVIPFWKLDLDQDYRVTCFTSWSPCFSCAQEMAKFISKNKHVSLCIFTARIY





RRQGRCQEGLRTLAEAGAKISIMTYSEFKHCWDTFVDHQGCPFQPWDGLDEHSQDLSGR





LRAILQSGSETPGTSESATPESDKKYSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDR





HSIKKNLIGALLFDSGETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDS FFHRL





EESFLVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYLALAHMI





KFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLE





NLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIG





DQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQL





PEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRT





FDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFAWMT





RKSEETITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTK





VKYVTEGMRKPAFLSGEQKKAIVDLLFKTNRKVTVKQLKEDYFKKIECFDSVETSGVEDR





FNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKV





MKQLKRRRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKED





IQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKPENIVIEMAREN





QTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQLQNEKLYLYYLQNGRDMYVDQ





ELDINRLSDYDVDHIVPQSFLKDDSIDNKVLTRSDKNRGKSDNVPSEEVVKKMKNYWRQ





LLNAKLITQRKFDNLTKAERGGLSELDKAGFIKRQLVETRQITKHVAQILDSRMNTKYDE





NDKLIREVKVITLKSKLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLE





SEFVYGDYKVYDVRKMIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGEIRKRPLIETN





GETGEIVWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFSKESILPKRNSDKLIARKKD





WDPKKYGGFDSPTVAYSVLVVAKVEKGKSKKLKSVKELLGITIMERSSFEKNPIDFLEAK





GYKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKL





KGSPEDNEQKQLFVEQHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQA





ENIIHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLDATLIHQSITGLYETRIDLSQLGGD





SGGSTNLSDIIEKETGKQLVIQESILMLPEEVEEVIGNKPESDILVHTAYDESTDENVMLLT





SDAPEYKPWALVIQDSNGENKIKMLSGGSPKKKRKV







Base Calling Matlab Script









(SEQ ID NO: 595)


WTnuc = ′GCGGACATGGAGGACGTGCGCGGCCGCCTGGTGCAGTACCGC





GGCGAGGTGCAGGCCATGCTCGGCCAGA





GCACCGAGGAGCTGCGGGTGCGCCTCGCCTCCCACCTGCGCAAGCTGCGT





AAGCGGCTCCTCCGCGATGCCGATGAC





CTGCAGAAGCGCCTGGCAGTGTACCAGGCCGGGGCCCGCGAGGGCGCCGA





GCGCGGCCTCAGCGCCATCCGCGAGCG CCTGGGGCCCCTGGTGGAACA





G′;



















%cycle through fastq files for different samples files=dir(‘*.fastq’);



for d=1:20



filename=files(d).name;



%read fastq file



[header,seqs,qscore]=fastqread(filename);



seqsLength=length(seqs);
   % number of sequences seqsFile=


strrep(filename,‘.fastq’,‘’);
   % trims off .fastq







%create a directory with the same name as fastq file ifexist(seqsFile,‘dir’);


 error(‘Directory already exists. Please rename or move it before moving on.’);








end



mkdir(seqsFile);
   % make directory


wtLength=length(WTnuc);
    % length of wildtype sequence


%% aligning back to the wildtype nucleotide sequence



%



% MN is a matrix of the nucleotide alignment window=1:wtLength;



sBLength=length(seqs);
  % number of sequences


% counts number of skips nSkips = 0;



ALN=repmat(‘’,[sBLengthwtLength]);



% iterate through each sequencing read for i = 1:sBLength



%If you only have forward read fastq files leave as is








%If you have R1 foward and R2 is reverse fastq files uncomment the








%next four lines of code and the subsequent end statement



%
ifmod(d,2)==0;


%
 reverse=seqrcomplement(seqs{i});


%
 [score,alignment,start]=


swalign(reverse,WTnuc,‘Alphabet’,‘NT’);



%
else


[score,alignment,start]=swalign(seqs{i},WTnuc,‘Alphabet’,‘NT’);



%
end


% length of the sequencing read len=



length(alignment(3,:));



% if there is a gap in the alignment, skip = 1 and we will



 % throw away the entire read skip = 0;



 for j = 1:len



if (alignment(3,j) == ‘−’|| alignment(1,j) == ‘−’) skip = 1;



     break;



 end



 %in addition if the qscore for any given base in the read is








    %below 31 the nucleotide is turned into an N (fastq qscores that are not letters)








 ifisletter(qscore{i}(start(1)+j−1)) else



 alignment(1,j) = ‘N’;



  end



 end



 if skip == 0 && len>10



 ALN(i, start(2):(start(2)+length(alignment)−1))=alignment(1,:);



   end



 end








% with the alignment matrices we can simply tally up the occurrences of








% each nucleotide at each column in the alignment these



% tallies ignore bases annotated as N



% due to low qscores



TallyNTD=zeros(5,wtLength); for i=1:wtLength








TallyNTD(:,i)=[sum(ALN(:,i)==‘A’),sum(ALN(:,i)==‘C’),sum(ALN(:,i)==‘G’),








sum(ALN(:,i)==‘T’),sum(ALN(:,i)==‘N’)];



end



% we then save these tally matrices in the respective folder for



% further processing








save(strcat(seqsFile,‘/TallyNTD’),‘TallyNTD’); dlmwrite(strcat(seqsFile,‘/TallyNTD.txt’),TallyNTD,‘precision’,








‘%.3f’,‘newline’,‘pc’); end











INDEL Detection Matlab Script









(SEQ ID NO: 595)


WTnuc = ′GCGGACATGGAGGACGTGCGCGGCCGCCTGGTGCAGTACCG





CGGCGAGGTGCAGGCCATGCTCGGCCAGA





GCACCGAGGAGCTGCGGGTGCGCCTCGCCTCCCACCTGCGCAAGCTGCGT





AAGCGGCTCCTCCGCGATGCCGATGAC





CTGCAGAAGCGCCTGGCAGTGTACCAGGCCGGGGCCCGCGAGGGCGCCGA





GCGCGGCCTCAGCGCCATCCGCGAGCG CCTGGGGCCCCTGGTGGAACA





G′;


















%cycle through fastq files for different samples files=dir(‘*.fastq’);


%specify start and width of indel window as well as length of each flank indelstart=154;








width=30; flank=10;



for d=1:3



filename=files(d).name;



%read fastq file



[header,seqs,qscore]=fastqread(filename);



seqsLength=length(seqs);
% number of sequences seqsFile


=strcat(strrep(filename,‘.fastq’,‘’),‘_INDELS’);








%create a directory with the same name as fastq file+_INDELS ifexist(seqsFile,‘dir’);


   error(‘Directory already exists. Please rename or move it before moving on.’);








end



mkdir(seqsFile);
% make directory


wtLength=length(WTnuc);
% length of wildtype sequence sBLength =


length(seqs);
% number of sequences


% initialize counters and cell arrays



nSkips = 0; notINDEL=0;



ins={ };



dels={ }; NumIns=0;



NumDels=0;








% iterate through each sequencing read for i = 1:sBLength


   %search for 10BP sequences that should flank both sides of the “INDEL WINDOW”


  windowstart=strfind(seqs{i},WTnuc(indelstart-flank:indelstart));


    windowend=strfind(seqs{i},WTnuc(indelstart+width:indelstart+width+flank








));



%if the flanks are found proceed



iflength(windowstart)==1&&length(windowend)==1



%if the sequence length matches the INDEL window length save as



 %not INDEL



if windowend-windowstart==width+flank notINDEL=notINDEL+1;



 %if the sequence is two or more bases longer than the INDEL



 %window length save as an Insertion



elseif windowend-windowstart>=width+flank+2 NumIns=NumIns+1;



 ins{NumDels}=seqs{i};



 %if the sequence is two or more bases shorter than the INDEL



 %window length save as a Deletion



elseif windowend-windowstart<=width+flank−2 NumDels=NumDels+1;



 dels{NumDels}=seqs{i};



 %keep track of skipped sequences that are either one base



 %shorter or longer than the INDEL window width else



 nSkips=nSkips+1;



 end



 %keep track of skipped sequences that do not possess matching flank



 %sequences else



 nSkips=nSkips+1;



  end



 end



 fid=fopen(strcat(seqsFile,‘/summary.txt’),‘wt’);








 fprintf(fid, ‘Skipped reads %i\n not INDEL %i\n Insertions %i\n Deletions








%i\n’, [nSkips, notINDEL, NumIns, NumDels]); fclose(fid);








 save(strcat(seqsFile,‘/nSkips’),‘nSkips’); save(strcat(seqsFile,‘/notINDEL’),‘notINDEL’);


 save(strcat(seqsFile,‘/NumIns’),‘NumIns’); save(strcat(seqsFile,‘/NumDels’),‘NumDels’);








 save(strcat(seqsFile,‘/dels’),‘dels’);



 C = dels;



 fid=fopen(strcat(seqsFile,‘/dels.txt’),‘wt’); fprintf(fid,‘“%s”\n’,C{:});



 fclose(fid);



 save(strcat(seqsFile,‘/ins’),‘ins’); C = ins;



 fid=fopen(strcat(seqsFile,‘/ins.txt’), ‘wt’); fprintf(fid,‘“%s”\n’,C{:});



 fclose(fid);



 end









Example 5: Cas9 Variant Sequences

The disclosure provides Cas9 variants, for example Cas9 proteins from one or more organisms, which may comprise one or more mutations (e.g., to generate dCas9 or Cas9 nickase). In some embodiments, one or more of the amino acid residues, identified below by an asterek, of a Cas9 protein may be mutated. In some embodiments, the D10 and/or H840 residues of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, are mutated. In some embodiments, the D10 residue of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, is mutated to any amino acid residue, except for D. In some embodiments, the D10 residue of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, is mutated to an A. In some embodiments, the H840 residue of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding residue in any of the amino acid sequences provided in SEQ ID NOs: 11-260, is an H. In some embodiments, the H840 residue of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, is mutated to any amino acid residue, except for H. In some embodiments, the H840 residue of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, is mutated to an A. In some embodiments, the D10 residue of the amino acid sequence provided in SEQ ID NO: 10, or a corresponding residue in any of the amino acid sequences provided in SEQ ID NOs: 11-260, is a D.


A number of Cas9 sequences from various species were aligned to determine whether corresponding homologous amino acid residues of D10 and H840 of SEQ ID NO: 10 or SEQ ID NO: 11 can be identified in other Cas9 proteins, allowing the generation of Cas9 variants with corresponding mutations of the homologous amino acid residues. The alignment was carried out using the NCBI Constraint-based Multiple Alignment Tool (COBALT(accessible at st-va.ncbi.nlm.nih.gov/tools/cobalt), with the following parameters. Alignment parameters: Gap penalties-11, -1; End-Gap penalties-5, -1. CDD Parameters: Use RPS BLAST on; Blast E-value 0.003; Find Conserved columns and Recompute on. Query Clustering Parameters: Use query clusters on; Word Size 4; Max cluster distance 0.8; Alphabet Regular.


An exemplary alignment of four Cas9 sequences is provided below. The Cas9 sequences in the alignment are: Sequence 1 (S1): SEQ ID NO: 11|WP_010922251| gi 499224711|type II CRISPR RNA-guided endonuclease Cas9 [Streptococcus pyogenes]; Sequence 2 (S2): SEQ ID NO: 12|WP_039695303|gi 746743737|type II CRISPR RNA-guided endonuclease Cas9 [Streptococcus gallolyticus]; Sequence 3 (S3): SEQ ID NO: 13|WP_045635197|gi 782887988|type II CRISPR RNA-guided endonuclease Cas9 [Streptococcus mitis]; Sequence 4 (S4): SEQ ID NO: 14|5AXW_A|gi 924443546|Staphylococcus aureus Cas9. The HNH domain (bold and underlined) and the RuvC domain (boxed) are identified for each of the four sequences. Amino acid residues 10 and 840 in S1 and the homologous amino acids in the aligned sequences are identified with an asterisk following the resective amino acid residue.













S1
1
--MDKK-YSIGLD*IGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLI--GALLEDSG--ETAEATRLKRTARRRYT
73






S2
1
--MTKKNYSIGLD*IGTNSVGWAVITDDYKVPAKKMKVLGNTDKKYIKKNLL--GALLFDSG--ETAEATRLKRTARRRYT
74





S3
1
--M-KKGYSIGLD*IGTNSVGFAVITDDYKVPSKKMKVLGNTDKRFIKKNLI--GALLFDEG--TTAEARRLKRTARRRYT
73





S4
1
GSHMKRNYILGLD*IGITSVGYGII--DYET-----------------RDVIDAGVRLFKEANVENNEGRRSKRGARRLKR
61





S1
74
RRKNRICYLQEIFSNEMAKVDDSFEHRLEESELVEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRL
153





S2
75
RRKNRLRYLQEIFANETAKVDESFFQRLDESFLTDDDKTEDSHPIFGNKAEEDAYHQKFPTIYHLRKHLADSSEKADLRL
154





S3
74
RRKNRLRYLQEIFSEEMSKVDSSFEHRLDDSFLIPEDKRESKYPIFATLTEEKEYHKQFPTIYHLRKQLADSKEKTDLRL
153





S4
62
RRRHRIQRVKKLL--------------FDYNLLTD--------------------HSELSGINPYEARVKGLSQKLSEEE
107





S1
154
IYLALAHNIKERGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPINASGVDAKAILSARLSKSRRLENLIAQLPGEK
233





S2
155
VYLALAHNIKERGHFLIEGELNAENTDVQKIFADFVGVYNRTFDDSHLSEITVDVASILTEKISKSRRLENLIKYYPTEK
234





S3
154
TYLALAHNIKYRGHFLYEEAFDIKNNDIQKIFNEFISIYDNTFEGSSLSGQNAQVEAIFTDKISKSAKRERVLKLEPDEK
233





S4
108
FSAALLHLAKRRG----------------------VHNVNEVEEDT----------------------------------
131





S1
234
KNGLFGNLIALSLGLTPNEKSNFDLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEIT
313





S2
235
KNTLFGNLIALALGLQPNEKTNFKLSEDAKLQFSKDTYEEDLEELLGKIGDDYADLFTSAKNLYDAILLSGILTVDDNST
314





S3
234
STGLFSEFLKLIVGNQADFKKHFDLEDKAPLQFSKDTYDEDLENLLGQIGDDFTDLFVSAKKLYDAILLSGILTVTDPST
313





S4
132
-----GNELS------------------TKEQISRN--------------------------------------------
144





S1
314
KAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSKNGYAGYIDGGASQEEFYKFIKPILEKM--DGTEELLV
391





S2
315
KAPLSASMIKRYVEHHEDLEKLKEFIKANKSELYHDIFKDKNKNGYAGYIENGVKQDEFYKYLKNILSKIKIDGSDYFLD
394





S3
314
KAPLSASMIERYENHQNDLAALKQFIKNNLPEKYDEVFSDQSKDGYAGYIDGKTTQETFYKYIKNLLSKF--EGTDYFLD
391





S4
145
----SKALEEKYVAELQ-------------------------------------------------LERLKKDG------
165





S1
392
KLNREDLLRKQRTFDNGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLARGNSRFAWMTRKSEE
471





S2
395
KIEREDFLRKQRTFDNGSIPHQIHLQEMHAILRRQGDYYPFLKEKQDRIEKILTFRIPYYVGPLVRKDSRFAWAEYRSDE
474





S3
392
KIEREDFLRKQRTFDNGSIPHQIHLQEMNAILRRQGEYYPFLKDNKEKIEKILTFRIPYYVGPLARGNRDFAWLTRNSDE
471





S4
166
--EVRGSINRFKTSD--------YVKEAKQLLKVQKAYHQLDQSFIDTYIDLLETRRTYYEGP--GEGSPFGW------K
227





S1
472
TITPWNFEEVVDKGASAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDL
551





S2
475
KITPWNFDKVIDKEKSAEKFITRMTLNDLYLPEEKVLPKHSHVYETYAVYNELTKIKYVNEQGKE-SFFDSNMKQEIFDH
553





S3
472
AIRPWNFEEIVDKASSAEDFINKMTNYDLYLPEEKVLPKHSLLYETFAVYNELTKVKFIAEGLRDYQFLDSGQKKQIVNQ
551





S4
228
DIKEW---------------YEMLMGHCTYFPEELRSVKYAYNADLYNALNDLNNLVITRDENEK---LEYYEKFQIIEN
289





S1
552
LEKTNRKVTVKQLKEDYFKKIECFDSVEISGVEDR---FNASLGTYHDLLKIIKDKDFLDNEENEDILEDIVLTLTLFED
628





S2
554
VFKENRKVTKEKLLNYLNKEFFEYRIKDLIGLDKENKSFNASLGTYHDLKKIL-DKAFLDDKVNEEVIEDIIKTLTLFED
632





S3
552
LEKENRKVTEKDIIHYLHN-VDGYDGIELKGIEKQ---FNASLSTYHDLLKIIKDKEENDDAKNEAILENIVHTLTIFED
627





S4
290
VFKQKKKPTLKQIAKEILVNEEDIKGYRVTSTGKPEF---TNLKVYHDIKDITARKEII---ENAELLDQIAKILTIYQS
363





S1
629
REMIEERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDKQSGKTILDFLKSDGFANRNFMQLIHDDSLTFKED
707





S2
633
KDMIHERLQKYSDIFTANQLKKLER-RHYTGWGRLSYKLINGIRNKENNKTILDYLIDDGSANRNFMQLINDDTLPFKQI
711





S3
628
REMIKQRLAQYDSLFDEKVIKALTR-RHYTGWGKLSAKLINGICDKQTGNTILDYLIDDGKINRNFMQLINDDGLSFKEI
706





S4
364
SEDIQEELTNLNSELTQEEIEQISNLKGYTGTHNLSLKAINLILDE------LWHTNDNQIAIFNRLKLVP---------
428





S1
708


embedded image


781





S2
712


embedded image


784





S3
707


embedded image


779





S4
429


embedded image


505





S1
782


KRIEEGIKELGSQIL-------KEHPVENTQLQNEKLYLYYLQNGRDMYVDQELDINRLSD----YDVDH*IVPQSFLKDD


850





S2
785


KKLQNSLKELGSNILNEEKPSYIEDKVENSHLQNDQLFLYYIQNGKDMYTGDELDIDHLSD----YDIDH*IIPQAFIKDD


860





S3
780


KRIEDSLKILASGL---DSNILKENPTDNNQLQNDRLFLYYLQNGKDMYTGEALDINQLSS----YDIDH*IIPQAFIKDD


852





S4
506


ERIEEIIRTTGK---------------ENAKYLIEKIKLHDMQEGKCLYSLEAIPLEDLLNNPFNYEVDH*IIPRSVSFDN


570





S1
851


embedded image


922





S2
861


embedded image


932





S3
853


embedded image


924





S4
571


embedded image


650





S1
923


embedded image


1002





S2
933


embedded image


1012





S3
925


embedded image


1004





S4
651


embedded image


712





S1
1003


embedded image


1077





S2
1013


embedded image


1083





S3
1005


embedded image


1081





S4
713


embedded image


764





S1
1078


embedded image


1149





S2
1084


embedded image


1158





S3
1082


embedded image


1156





S4
765


embedded image


835





S1
1150
EKGKSKKLKSVKELLGITIMERSSFEKNPI-DFLEAKG-----YKEVKKDLIIKLPKYSLFELENGRKRMLASAGELQKG
1223





S2
1159
EKGKAKKLKTVKELVGISIMERSFFEENPV-EFLENKG-----YHNIREDKLIKLPKYSLFEFEGGRRRLLASASELQKG
1232





S3
1157
EKGKAKKLKTVKTLVGITIMEKAAFEENPI-TFLENKG-----YHNVRKENILCLPKYSLFELENGRRRLLASAKELQKG
1230





S4
836
DPQTYQKLK--------LIMEQYGDEKNPLYKYYEETGNYLTKYSKKDNGPVIKKIKYYGNKLNAHLDITDDYPNSRNKV
907





S1
1224
NELALPSKYVNFLYLASHYEKLKGSPEDNEQKQLFVEQHKHYLDEITEQISEFSKRVILADANLDKVLSAYNKH------
1297





S2
1233
NEMVLPGYLVELLYHAHRADNF-----NSTEYLNYVSEHKKEFEKVLSCVEDFANLYVDVEKNLSKIRAVADSM------
1301





S3
1231
NEIVLPVYLTTLLYHSKNVHKL-----DEPGHLEYIQKHRNEFKDLLNLVSEFSQKYVLADANLEKIKSLYADN------
1299





S4
908
VKLSLKPYRFD-VYLDNGVYKFV-----TVKNLDVIK--KENYYEVNSKAYEEAKKLKKISNQAEFIASFYNNDLIKING
979





S1
1298
RDKPIREQAENITHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLDATLIHQSIT--------GLYETRI----DLSQL
1365





S2
1302
DNFSIEEISNSFINLLTLTALGAPADFNFLGEKIPRKRYTSTKECLNATLIHQSIT--------GLYETRI----DLSKL
1369





S3
1300
EQADIEILANSFINLLTFTALGAPAAFKFFGKDIDRKRYTTVSEILNATLIHQSIT--------GLYETWI----DLSKL
1367





S4
980
ELYRVIGVNNDLLNRIEVNMIDITYR-EYLENMNDKRPPRIIKTIASKT---QSIKKYSTDILGNLYEVKSKKHPQIIKK
1055





S1
1366
GGD
1368





S2
1370
GEE
1372





S3
1368
GED
1370





S4
1056
G--
1056






The alignment demonstrates that amino acid sequences and amino acid residues that are homologous to a reference Cas9 amino acid sequence or amino acid residue can be identified across Cas9 sequence variants, including, but not limited to Cas9 sequences from different species, by identifying the amino acid sequence or residue that aligns with the reference sequence or the reference residue using alignment programs and algorithms known in the art. This disclosure provides Cas9 variants in which one or more of the amino acid residues identified by an asterisk in SEQ ID NOs: 11-14 (e.g., S1, S2, S3, and S4, respectively) are mutated as described herein. The residues D10 and H840 in Cas9 of SEQ ID NO: 10 that correspond to the residues identified in SEQ ID NOs: 11-14 by an asterisk are referred to herein as “homologous” or “corresponding” residues. Such homologous residues can be identified by sequence alignment, e.g., as described above, and by identifying the sequence or residue that aligns with the reference sequence or residue. Similarly, mutations in Cas9 sequences that correspond to mutations identified in SEQ ID NO: 10 herein, e.g., mutations of residues 10, and 840 in SEQ ID NO: 10, are referred to herein as “homologous” or “corresponding” mutations. For example, the mutations corresponding to the D10A mutation in SEQ ID NO: 10 or S1 (SEQ ID NO: 11) for the four aligned sequences above are D11A for S2, D10A for S3, and D13A for S4; the corresponding mutations for H840A in SEQ ID NO: 10 or S1 (SEQ ID NO: 11) are H850A for S2, H842A for S3, and H560A for S4.


A total of 250 Cas9 sequences (SEQ ID NOs: 11-260) from different species were aligned using the same algorithm and alignment parameters outlined above. Amino acid residues homologous to residues 10, and 840 of SEQ ID NO: 10 were identified in the same manner as outlined above. The alignments are provided below. The HNH domain (bold and underlined) and the RuvC domain (boxed) are identified for each of the four sequences. Single residues corresponding to amino acid residues 10, and 840 in SEQ ID NO: 10 are boxed in SEQ ID NO: 11 in the alignments, allowing for the identification of the corresponding amino acid residues in the aligned sequences.
















WP_010922251.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 11


WP_039695303.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusgallolyticus]
SEQ ID NO: 12


WP_045635197.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmitis]
SEQ ID NO: 13


5AXW_A
Cas9, Chain A, Crystal Structure [StaphylococcusAureus]
SEQ ID NO: 14


WP_009880683.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 15


WP_010922251.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 16


WP_011054416.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 17


WP_011284745.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 18


WP_011285506.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 19


WP_011527619.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 20


WP_012560673.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 21


WP_014407541.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 22


WP_020905136.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 23


WP_023080005.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 24


WP_023610282.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 25


WP_030125963.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 26


WP_030126706.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 27


WP_031488318.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 28


WP_032460140.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 29


WP_032461047.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 30


WP_032462016.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 31


WP_032462936.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 32


WP_032464890.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 33


WP_033888930.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 34


WP_038431314.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 35


WP_038432938.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 36


WP_038434062.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspyogenes]
SEQ ID NO: 37


BAQ51233.1
CRISPR-associated protein, Csn1 family [Streptococcuspyogenes]
SEQ ID NO: 38


KGE60162.1
hypothetical protein MGAS2111_0903 [Streptococcuspyogenes MGAS2111]
SEQ ID NO: 39


KGE60856.1
CRISPR-associated endonuclease protein [Streptococcuspyogenes SS1447]
SEQ ID NO: 40


WP_002989955.1
MULTISPECIES: type II CRISPR RNA-guided endonuclease Cas9 [Streptococcus]
SEQ ID NO: 41


WP_003030002.1
MULTISPECIES: type II CRISPR RNA-guided endonuclease Cas9 [Streptococcus]
SEQ ID NO: 42


WP_003065552.1
MULTISPECIES: type II CRISPR RNA-guided endonuclease Cas9 [Streptococcus]
SEQ ID NO: 43


WP_001040076.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 44


WP_001040078.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 45


WP_001040080.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 46


WP_001040081.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 47


WP_001040083.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 48


WP_001040085.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 49


WP_001040087.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 50


WP_001040088.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 51


WP_001040089.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 52


WP_001040090.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 53


WP_001040091.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 54


WP_001040092.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 55


WP_001040094.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 56


WP_001040095.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 57


WP_001040096.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 58


WP_001040097.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 59


WP_001040098.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 60


WP_001040099.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 61


WP_001040100.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 62


WP_001040104.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 63


WP_001040105.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 64


WP_001040106.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 65


WP_001040107.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 66


WP_001040108.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 67


WP_001040109.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 68


WP_001040110.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 69


WP_015058523.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 70


WP_017643650.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 71


WP_017647151.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 72


WP_017648376.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 73


WP_017649527.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 74


WP_017771611.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 75


WP_017771984.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 76


CFQ25032.1
CRISPR-associated protein [Streptococcusagalactiae]
SEQ ID NO: 77


CFV16040.1
CRISPR-associated protein [Streptococcusagalactiae]
SEQ ID NO: 78


KLJ37842.1
CRISPR-associated protein Csn1 [Streptococcusagalactiae]
SEQ ID NO: 79


KLJ72361.1
CRISPR-associated protein Csn1 [Streptococcusagalactiae]
SEQ ID NO: 80


KLL20707.1
CRISPR-associated protein Csn1 [Streptococcusagalactiae]
SEQ ID NO: 81


KLL42645.1
CRISPR-associated protein Csn1 [Streptococcusagalactiae]
SEQ ID NO: 82


WP_047207273.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 83


WP_047209694.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 84


WP_050198062.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 85


WP_050201642.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 86


WP_050204027.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 87


WP_050881965.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 88


WP_050886065.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusagalactiae]
SEQ ID NO: 89


AHN30376.1
CRISPR-associated protein Csn1 [Streptococcusagalactiae 138P]
SEQ ID NO: 90


EAO78426.1
reticulocyte binding protein [Streptococcusagalactiae H36B]
SEQ ID NO: 91


CCW42055.1
CRISPR-associated protein, SAG0894 family [Streptococcusagalactiae ILRI112]
SEQ ID NO: 92


WP_003041502.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusanginosus]
SEQ ID NO: 93


WP_037593752.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusanginosus]
SEQ ID NO: 94


WP_049516684.1
CRISPR-associated protein Csn1 [Streptococcusanginosus]
SEQ ID NO: 95


GAD46167.1
hypothetical protein ANG6_0662 [Streptococcusanginosus T5]
SEQ ID NO: 96


WP_018363470.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuscaballi]
SEQ ID NO: 97


WP_003043819.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuscanis]
SEQ ID NO: 98


WP_006269658.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusconstellatus]
SEQ ID NO: 99


WP_048800889.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusconstellatus]
SEQ ID NO: 100


WP_012767106.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusdysgalactiae]
SEQ ID NO: 101


WP_014612333.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusdysgalactiae]
SEQ ID NO: 102


WP_015017095.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusdysgalactiae]
SEQ ID NO: 103


WP_015057649.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusdysgalactiae]
SEQ ID NO: 104


WP_048327215.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusdysgalactiae]
SEQ ID NO: 105


WP_049519324.1
CRISPR-associated protein Csn1 [Streptococcusdysgalactiae]
SEQ ID NO: 106


WP_012515931.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusequi]
SEQ ID NO: 107


WP_021320964.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusequi]
SEQ ID NO: 108


WP_037581760.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusequi]
SEQ ID NO: 109


WP_004232481.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusequinus]
SEQ ID NO: 110


WP_009854540.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusgallolyticus]
SEQ ID NO: 111


WP_012962174.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusgallolyticus]
SEQ ID NO: 112


WP_039695303.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusgallolyticus]
SEQ ID NO: 113


WP_014334983.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusinfantarius]
SEQ ID NO: 114


WP_003099269.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusiniae]
SEQ ID NO: 115


AHY15608.1
CRISPR-associated protein Csn1 [Streptococcusiniae]
SEQ ID NO: 116


AHY17476.1
CRISPR-associated protein Csn1 [Streptococcusiniae]
SEQ ID NO: 117


ESR09100.1
hypothetical protein IUSA1_08595 [Streptococcusiniae IUSA1]
SEQ ID NO: 118


AGM98575.1
CRISPR-associated protein Cas9/Csn1, subtype II/NMEMI [Streptococcusiniae SF1]
SEQ ID NO: 119


ALF27331.1
CRISPR-associated protein Csn1 [Streptococcusintermedius]
SEQ ID NO: 120


WP_018372492.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmassiliensis]
SEQ ID NO: 121


WP_045618028.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmitis]
SEQ ID NO: 122


WP_045635197.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmitis]
SEQ ID NO: 123


WP_002263549.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 124


WP_002263887.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 125


WP_002264920.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 126


WP_002269043.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 127


WP_002269448.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 128


WP_002271977.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 129


WP_002272766.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 130


WP_002273241.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 131


WP_002275430.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 132


WP_002276448.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 133


WP_002277050.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 134


WP_002277364.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 135


WP_002279025.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 136


WP_002279859.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 137


WP_002280230.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 138


WP_002281696.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 139


WP_002282247.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 140


WP_002282906.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 141


WP_002283846.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 142


WP_002287255.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 143


WP_002288990.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 144


WP_002289641.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 145


WP_002290427.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 146


WP_002295753.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 147


WP_002296423.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 148


WP_002304487.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 149


WP_002305844.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 150


WP_002307203.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 151


WP_002310390.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 152


WP_002352408.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 153


WP_012997688.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 154


WP_014677909.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 155


WP_019312892.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 156


WP_019313659.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 157


WP_019314093.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 158


WP_019315370.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 159


WP_019803776.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 160


WP_019805234.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 161


WP_024783594.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 162


WP_024784288.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 163


WP_024784666.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 164


WP_024784894.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 165


WP_024786433.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusmutans]
SEQ ID NO: 166


WP_049473442.1
CRISPR-associated protein Csn1 [Streptococcusmutans]
SEQ ID NO: 167


WP_049474547.1
CRISPR-associated protein Csn1 [Streptococcusmutans]
SEQ ID NO: 168


EMC03581.1
hypothetical protein SMU69_09359 [Streptococcusmutans NLML4]
SEQ ID NO: 169


WP_000428612.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusoralis]
SEQ ID NO: 170


WP_000428613.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusoralis]
SEQ ID NO: 171


WP_049523028.1
CRISPR-associated protein Csn1 [Streptococcusparasanguinis]
SEQ ID NO: 172


WP_003107102.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusparauberis]
SEQ ID NO: 173


WP_054279288.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcusphocae]
SEQ ID NO: 174


WP_049531101.1
CRISPR-associated protein Csn1 [Streptococcuspseudopneumoniae]
SEQ ID NO: 175


WP_049538452.1
CRISPR-associated protein Csn1 [Streptococcuspseudopneumoniae]
SEQ ID NO: 176


WP_049549711.1
CRISPR-associated protein Csn1 [Streptococcuspseudopneumoniae]
SEQ ID NO: 177


WP_007896501.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcuspseudoporcinus]
SEQ ID NO: 178


EFR44625.1
CRISPR-associated protein, Csn1 family [Streptococcuspseudoporcinus SPIN 20026]
SEQ ID NO: 179


WP_002897477.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcussanguinis]
SEQ ID NO: 180


WP_002906454.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcussanguinis]
SEQ ID NO: 181


WP_009729476.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcus sp. F0441]
SEQ ID NO: 182


CQR24647.1
CRISPR-associated protein [Streptococcus sp. FF10]
SEQ ID NO: 183


WP_000066813.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcus sp. M334]
SEQ ID NO: 184


WP_009754323.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcus sp. taxon 056]
SEQ ID NO: 185


WP_044674937.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcussuis]
SEQ ID NO: 186


WP_044676715.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcussuis]
SEQ ID NO: 187


WP_044680361.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcussuis]
SEQ ID NO: 188


WP_044681799.1
type II CRISPR RNA-guided endonuclease Cas9 [Streptococcussuis]
SEQ ID NO: 189


WP_049533112.1
CRISPR-associated protein Csn1 [Streptococcussuis]
SEQ ID NO: 190


WP_029090905.1
type II CRISPR RNA-guided endonuclease Cas9 [Brochothrixthermosphacta]
SEQ ID NO: 191


WP_006506696.1
type II CRISPR RNA-guided endonuclease Cas9 [Catenibacteriummitsuokai]
SEQ ID NO: 192


AIT42264.1
Cas9hc:NLS:HA [Cloning vector pYB196]
SEQ ID NO: 193


WP_034440723.1
type II CRISPR endonuclease Cas9 [Clostridialesbacterium S5-A11]
SEQ ID NO: 194


AKQ21048.1
Cas9 [CRISPR-mediated gene targeting vector p(bh5p68-Cas9)]
SEQ ID NO: 195


WP_004636532.1
type II CRISPR RNA-guided endonuclease Cas9 [Dolosigranulumpigrum]
SEQ ID NO: 196


WP_002364836.1
MULTISPECIES: type II CRISPR RNA-guided endonuclease Cas9 [Enterococcus]
SEQ ID NO: 197


WP_016631044.1
MULTISPECIES: type II CRISPR RNA-guided endonuclease Cas9 [Enterococcus]
SEQ ID NO: 198


EMS75795.1
hypothetical protein H318_06676 [Enterococcusdurans IPLA 655]
SEQ ID NO: 199


WP_002373311.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecalis]
SEQ ID NO: 200


WP_002378009.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecalis]
SEQ ID NO: 201


WP_002407324.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecalis]
SEQ ID NO: 202


WP_002413717.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecalis]
SEQ ID NO: 203


WP_010775580.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecalis]
SEQ ID NO: 204


WP_010818269.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecalis]
SEQ ID NO: 205


WP_010824395.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecalis]
SEQ ID NO: 206


WP_016622645.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecalis]
SEQ ID NO: 207


WP_033624816.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecalis]
SEQ ID NO: 208


WP_033625576.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecalis]
SEQ ID NO: 209


WP_033789179.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecalis]
SEQ ID NO: 210


WP_002310644.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecium]
SEQ ID NO: 211


WP_002312694.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecium]
SEQ ID NO: 212


WP_002314015.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecium]
SEQ ID NO: 213


WP_002320716.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecium]
SEQ ID NO: 214


WP_002330729.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecium]
SEQ ID NO: 215


WP_002335161.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecium]
SEQ ID NO: 216


WP_002345439.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecium]
SEQ ID NO: 217


WP_034867970.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecium]
SEQ ID NO: 218


WP_047937432.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusfaecium]
SEQ ID NO: 219


WP_010720994.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcushirae]
SEQ ID NO: 220


WP_010737004.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcushirae]
SEQ ID NO: 221


WP_034700478.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcushirae]
SEQ ID NO: 222


WP_007209003.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusitalicus]
SEQ ID NO: 223


WP_023519017.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusmundtii]
SEQ ID NO: 224


WP_010770040.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusphoeniculicola]
SEQ ID NO: 225


WP_048604708.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcus sp. AM1]
SEQ ID NO: 226


WP_010750235.1
type II CRISPR RNA-guided endonuclease Cas9 [Enterococcusvillorum]
SEQ ID NO: 227


AII16583.1
Cas9 endonuclease [Expression vector pCas9]
SEQ ID NO: 228


WP_029073316.1
type II CRISPR RNA-guided endonuclease Cas9 [Kandleriavitulina]
SEQ ID NO: 229


WP_031589969.1
type II CRISPR RNA-guided endonuclease Cas9 [Kandleriavitulina]
SEQ ID NO: 230


KDA45870.1
CRISPR-associated protein Cas9/Csn1, subtype II/NMEMI [Lactobacillusanimalis]
SEQ ID NO: 231


WP_039099354.1
type II CRISPR RNA-guided endonuclease Cas9 [Lactobacilluscurvatus]
SEQ ID NO: 232


AKP02966.1
hypothetical protein ABB45_04605 [Lactobacillusfarciminis]
SEQ ID NO: 233


WP_010991369.1
type II CRISPR RNA-guided endonuclease Cas9 [Listeriainnocua]
SEQ ID NO: 234


WP_033838504.1
type II CRISPR RNA-guided endonuclease Cas9 [Listeriainnocua]
SEQ ID NO: 235


EHN60060.1
CRISPR-associated protein, Csn1 family [Listeriainnocua ATCC 33091]
SEQ ID NO: 236


EFR89594.1
crispr-associated protein, Csn1 family [Listeriainnocua FSL S4-378]
SEQ ID NO: 237


WP_038409211.1
type II CRISPR RNA-guided endonuclease Cas9 [Listeriaivanovii]
SEQ ID NO: 238


EFR95520.1
crispr-associated protein Csn1 [Listeriaivanovii FSL F6-596]
SEQ ID NO: 239


WP_003723650.1
type II CRISPR RNA-guided endonuclease Cas9 [Listeriamonocytogenes]
SEQ ID NO: 240


WP_003727705.1
type II CRISPR RNA-guided endonuclease Cas9 [Listeriamonocytogenes]
SEQ ID NO: 241


WP_003730785.1
type II CRISPR RNA-guided endonuclease Cas9 [Listeriamonocytogenes]
SEQ ID NO: 242


WP_003733029.1
type II CRISPR RNA-guided endonuclease Cas9 [Listeriamonocytogenes]
SEQ ID NO: 243


WP_003739838.1
type II CRISPR RNA-guided endonuclease Cas9 [Listeriamonocytogenes]
SEQ ID NO: 244


WP_014601172.1
type II CRISPR RNA-guided endonuclease Cas9 [Listeriamonocytogenes]
SEQ ID NO: 245


WP_023548323.1
type II CRISPR RNA-guided endonuclease Cas9 [Listeriamonocytogenes]
SEQ ID NO: 246


WP_031665337.1
type II CRISPR RNA-guided endonuclease Cas9 [Listeriamonocytogenes]
SEQ ID NO: 247


WP_031669209.1
type II CRISPR RNA-guided endonuclease Cas9 [Listeriamonocytogenes]
SEQ ID NO: 248


WP_033920898.1
type II CRISPR RNA-guided endonuclease Cas9 [Listeriamonocytogenes]
SEQ ID NO: 249


AKI42028.1
CRISPR-associated protein [Listeriamonocytogenes]
SEQ ID NO: 250


AKI50529.1
CRISPR-associated protein [Listeriamonocytogenes]
SEQ ID NO: 251


EFR83390.1
crispr-associated protein Csn1 [Listeriamonocytogenes FSL F2-208]
SEQ ID NO: 252


WP_046323366.1
type II CRISPR RNA-guided endonuclease Cas9 [Listeriaseeligeri]
SEQ ID NO: 253


AKE81011.1
Cas9 [Plant multiplex genome editing vector pYLCRISPR/Cas9Pubi-H]
SEQ ID NO: 254


CUO82355.1
Uncharacterized protein conserved in bacteria [Roseburiahominis]
SEQ ID NO: 255


WP_033162887.1
type II CRISPR RNA-guided endonuclease Cas9 [Sharpeaazabuensis]
SEQ ID NO: 256


AGZ01981.1
Cas9 endonuclease [synthetic construct]
SEQ ID NO: 257


AKA60242.1
nuclease deficient Cas9 [synthetic construct]
SEQ ID NO: 258


AK540380.1
Cas9 [Synthetic plasmid pFC330]
SEQ ID NO: 259


4UN5_B
Cas9, Chain B, Crystal Structure
SEQ ID NO: 260













WP_010922251
1
MDKK-custom character A--EATRLKRTARRRYT
73


WP_039695303
1
MTKKnYSIGLDIGTNSVGWAVITDDYKVPAKKMKVLGNTDKKYIKKNLLGALLFDSGETA--EATRLKRTARRRYT
74


WP_045635197
1
K-KG-YSIGLDIGTNSVGFAVITDDYKVPSKKMKVLGNTDKRFIKKNLIGALLFDEGTTA--EARRLKRTARRRYT
73


5AXW_A
1
MKRN-YILGLDIGITSVGYGII--DYET------------RDVIDA---GVRLFKEANVEnnEGRRSKRGARRLKR
61


WP_009880683

----------------------------------------------------------------------------



WP_010922251
1
MDKK-YSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_011054416
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKLKGLGNTDRHGIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_011284745
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_011285506
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_011527619
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGEIA--EATRLKRTARRRYT
73


WP_012560673
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_014407541
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFGSGETA--EATRLKRTARRRYT
73


WP_020905136
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_023080005
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKLKVLGNTDRHGIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_023610282
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKLKVLGNTDRHGIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_030125963
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_030126706
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHGIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_031488318
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_032460140
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_032461047
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTERHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_032462016
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTERHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_032462936
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTERHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_032464890
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTERHSIKKNLIGALLFDSGEIA--EATRLKRTARRRYT
73


WP_033888930

----------------------------------------------------------------------------



WP_038431314
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_038432938
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_038434062
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


BAQ51233

----------------------------------------------------------------------------



KGE60162

----------------------------------------------------------------------------



KGE60856

----------------------------------------------------------------------------



WP_002989955
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGEIA--EATRLKRTARRRYT
73


WP_003030002
1
MDQK-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKQSIKKNLLGALLFDSGETA--EATRLKRTARRRYT
73


WP_003065552
1
MTKKnYSIGLDIGTNSVGWAVITDDYKVPAKKMKVLGNTDKKYIKKNLLGALLFDSGETA--EATRLKRTARRRYT
74


WP_001040076
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKIRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040078
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040080
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040081
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040083
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040085
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040087
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040088
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040089
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040090
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040091
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040092
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040094
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040095
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040096
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040097
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040098
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040099
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040100
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040104
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_001040105
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTSRRRYT
73


WP_001040106
1
MNKP-YSIGLDIGTNSVGYSVVTDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--SDRRLKRTARRRYT
73


WP_001040107
1
MNKP-YSIGLDIGTNSVGYSVVTDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--SDRRLKRTARRRYT
73


WP_001040108
1
MNKP-YSIGLDIGTNSVGYSVVTDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--SDRRLKRTARRRYT
73


WP_001040109
1
MNKP-YSIGLDIGTNSVGYSVVTDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--SDRRLKRTARRRYT
73


WP_001040110
1
MNKP-YSIGLDIGTNSVGYSVVTDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--SDRRLKRTARRRYT
73


WP_015058523
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_017643650
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_017647151
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--SDRRLKRTARRRYT
73


WP_017648376
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--SDRRLKRTARRRYT
73


WP_017649527
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_017771611
1
MNKP-YSIGLDIGTNSVGYSVVTDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--SDRRLKRTARRRYT
73


WP_017771984
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


CFQ25032
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


CFV16040
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


KLJ37842
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


KLJ72361
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


KLL20707
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


KLL42645
1
MNKP-YSIGLDIGTNSVGYSVVTDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--SDRRLKRTARRRYT
73


WP_047207273
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGRNTA--ADRRLKRTARRRYT
73


WP_047209694
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_050198062
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_050201642
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_050204027
1
MNKP-YSIGLDIGTNSVGYSVVTDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--SDRRLKRTARRRYT
73


WP_050881965
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


WP_050886065
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


AHN30376
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


EAO78426
1
MNKP-YSIGXDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRTARRRYT
73


CCW42055
1
MNKP-YSIGLDIGTNSVGWSIITDDYKVPAKKMRVLGNTDKEYIKKNLIGALLFDGGNTA--ADRRLKRIARRRYT
73


WP_003041502
1
MNQK-YSIGLDIGTNSVGWAVITDDYKVPAKKMKVLGNTDKQSIKKNLLGALLFDSGETA--EATRLKRTARRRYT
73


WP_037593752
1
MKKE-YSIGLDIGTNSVGWAVITDDYKVPAKKMKVLGNTDKQSIKKNLLGALLFDSGETA--EATRLKRTARRRYT
74


WP_049516684
1
MKKE-YSIGLDIGTNSVGWAVITDDYKVPAKKMKVLGNTDKQSIKKNLLGALLFDSGETA--EATRLKRTARRRYT
74


GAD46167
1
MKKE-YSIGLDIGTNSVGWAVITDDYKVPAKKMKVLGNTDKQSIKKNLLGALLFDSGETA--EATRLKRTARRRYT
73


WP_018363470
1
MTKKnYSIGLDIGTNSVGWAVITDDYKVPAKKMKVLGNTDKKYIKKNLLGALLFDSGETA--EATRLKRTARRRYT
74


WP_003043819
1
MEKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTNRKSIKKNLMGALLFDSGETA--EATRLKRTARRRYT
73


WP_006269658
1
MGKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKQSIKKNLLGALLFDSGETA--EATRLKRTARRRYT
73


WP_048800889
1
MTQK-YSIGLDIGTNSVGWAIVTDDYKVPAKKMKILGNTNKQYIKKNLLGALLFDSGETA--KATRLKRTARRRYT
73


WP_012767106
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_014612333
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_015017095
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_015057649
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_048327215
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_049519324
1
MDKK-YSIGLDIGTNSVGWAVITDDYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_012515931
1
MKKP-YTIALDIGTNSVGWVVVTDDYRVPTKKMKVLGNTERKTIKKNLIGALLFDSGETA--EGTRLKRTARRRYT
73


WP_021320964
1
MKKP-YTIALDIGTNSVGWVVVTDDYRVPTKKMKVLGNTERKTIKKNLIGALLFDSGETA--EGTRLKRTARRRYT
73


WP_037581760
1
MKKP-YTIALDIGTNSVGWVVVTDDYRVPTKKMKVLGNTERKTIKKNLIGALLFDSGETA--EGTRLKRTARPRYT
73


WP_004232481
1
M-EKtYSIGLDIGTNSVGWAVITDDYKVPAKKMKVLGNTDKKYIKKNLLGALLFDSGETA--EATRLKRAARRRYT
73


WP_009854540
1
MTKKnYSIGLDIGTNSVGWAVITDDYKVPAKKMKVLGNTDKKYIKKNLLGALLFDSGETA--EATRLKRTARRRYT
74


WP_012962174
1
MTEKnYSIGLDIGTNSVGWAVITDDYKVPAKKMKVLGNTDKKYIKKNLLGALLFDNGETA--EATRLKRTARRRYT
74


WP_039695303
1
MTKKnYSIGLDIGTNSVGWAVITDDYKVPAKKMKVLGNTDKKYIKKNLLGALLFDSGETA--EATRLKRTARRRYT
74


WP_014334983
1
M-EKsYSIGLDIGTNSVGWAVITDDYKVPAKKMKVLGNTDKKYIKKNLLGALLFDSGETA--EVTRLKRTARRRYT
73


WP_003099269
1
MRKP-YSIGLDIGTNSVGWAVITDDYKVPSKKMRIQGTTDRTSIKKNLIGALLFDNGETA--EATRLKRTTRRRYT
73


AHY15608
1
MRKP-YSIGLDIGTNSVGWAVITDDYKVPSKKMRIQGTTDRTSIKKNLIGALLFDNGETA--EATRLKRTTRRRYT
73


AHY17476
1
MRKP-YSIGLDIGTNSVGWAVITDDYKVPSKKMRIQGTTDRTSIKKNLIGALLFDNGETA--EATRLKRTTRRRYT
73


ESR09100

----------------------------------------------------------------------------



AGM98575
1
MRKP-YSIGLDIGTNSVGWAVITDDYKVPSKKMRIQGTTDRTSIKKNLIGALLFDNGETA--EATRLKRTTRRRYT
73


ALF27331
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_018372492
1
MKKP-YSIGLDIGTNSVGWAVVMEDYKVPSKKMKVLGNTDKQSIKKNLIGALLFDSGETAv--ERRLNRTTSRRYD
73


WP_045618028
1
NNKP-YSIGLDIGTNSVGWAVITDDYKVPSKKMKVLGNTDKHFIKKNLLGALLFDEGTTA--EDRRLKRTARRRYT
74


WP_045635197
1
K-KG-YSIGLDIGTNSVGFAVITDDYKVPSKKMKVLGNTDKRFIKKNLIGALLFDEGTTA--EARRLKRTARRRYT
73


WP_002263549
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIEKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002263887
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIEKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002264920
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002269043
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002269448
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002271977
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002272766
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002273241
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002275430
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--ADRRLKRTARRRYT
73


WP_002276448
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002277050
1
MKKS-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002277364
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--ADRRLKRTARRRYT
73


WP_002279025
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIEKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002279859
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002280230
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--ADRRLKRTARRRYT
73


WP_002281696
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--ADRRLKRTARRRYT
73


WP_002282247
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002282906
1
MKKP-YSIGLDIGTNSVGWSVVTDDYKVPAKKMKVLGNTDKSHIEKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002283846
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002287255
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVSAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002288990
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002289641
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTTRRRYT
73


WP_002290427
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002295753
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002296423
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002304487
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002305844
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002307203
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002310390
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_002352408
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_012997688
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--ADRRLKRTARRRYT
73


WP_014677909
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPDKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_019312892
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--ADRRLKRTARRRYT
73


WP_019313659
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIEKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_019314093
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_019315370
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_019803776
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIEKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_019805234
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_024783594
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIEKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_024784288
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTARRRYT
73


WP_024784666
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--ADRRLKRTARRRYT
73


WP_024784894
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTTRRRYT
73


WP_024786433
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--ADRRLKRTARRRYT
73


WP_049473442
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--ADRRLKRTARRRYT
73


WP_049474547
1
MKKP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--EDRRLKRTTRRRYT
73


EMC03581
1
MDL--------IGTNSVGWAVVTDDYKVPAKKMKVLGNTDKSHIKKNLLGALLFDSGNTA--ADRRLKRTARRRYT
66


WP_000428612
1
ENKN-YSIGLDIGTNSVGWAVITDDYKVPSKKMKVLGNTDKRFIKKNLIGALLFDEGTTA--EARRLKRTARRRYT
74


WP_000428613
1
ENKN-YSIGLDIGTNSVGWSVITDDYKVPSKKMKVLGNTDKRFIKKNLIGALLFDEGTTA--EARRLKRTARRRYT
74


WP_049523028
1
K-KP-YSIGLDIGTNSVGWAVITDDYKVPAKKMKVLGNTNKESIKKNLIGALLFDAGNTA--ADRRLKRTARRRYT
73


WP_003107102
1
--------------------------------MKVLGNTDRQTVKKNMIGTLLFDSGETA--EARRLKRTARRRYT
42


WP_054279288
1
-KKS-YSIGLDIGTNSVGWAVITDDYKVPAKKMKVLGNTSRQSIKKNMIGALLFDEGGPA--ASTRVKRTTRRRYT
75


WP_049531101
1
SNKP-YSIGLDIGTNSVGWAVITDDYKVPSKKMKVLGNTDKHFIKKNLIGALLFDEGTTA--EDRRLKRTARRRYT
74


WP_049538452
1
SNKP-YSIGLDIGTNSVGWVIITDDYKVPSKKMKVLGNTDKHFIKKNLIGALLFDEGTTA--EDRRLKRTARRRYT
74


WP_049549711
1
SNKP-YSIGLDIGTNSVGWAVITDDYKVPSKKMTVLGNTDKHFIKKNLIGALLFDEGTTA--EDRRLKRTARRRYT
74


WP_007896501
1
--YS-YSIGLDIGTNSVGWAVINEDYKVPAKKMTVFGNTDRKTIKKNLLGTVLFDSGETA--QARRLKRTNRRRYT
75


EFR44625
1
-----------------------------------------------MLGTVLFDSGETA--QARRLKRTNRRRYT
27


WP_002897477
1
K-KP-YSIGLDIGTNSVGWAVVTDDYKVPAKKMRVFGDTDRSHIKKNLLGTLLFDDGNTA--ESRRLKRTARRRYT
73


WP_002906454
1
K-KP-YSIGLDIGTNSVGWAVITDDYKVPSKKMKVLGNTDKHFIKKNLIGALLFDEGTTA--EDRRLKRTSRRRYT
73


WP_009729476
1
ENKN-YSIGLDIGTNSVGWSVITDDYKVPSKKMKVLGNTDKHFIKKNLIGALLFDEGTTA--EARRLKRTARRRYT
74


CQR24647
1
MKKP-YSIGLDIGTNSVGWSVVTDDYKVPAKKMKVLGNTDKEYIKKNLIGALLFDSGETA--EATRMKRTARRRYT
73


WP_000066813
1
SNKS-YSIGLDIGTNSVGWAVITDDYKVPSKKMKVLGNTDKHFIKKNLIGALLFDEGTTA--EDRRLKRTARRRYT
74


WP_009754323
1
NNNN-YSIGLDIGTNSVGWAVITDDYKVPSKKMRVLGNTDKRFIKKNLIGALLFDEGTTA--EDRRLKRTARRRYT
74


WP_044674937
1
MKKK-YAIGIDIGTNSVGWSVVTDDYKVPSKKMKVFGNTEKRYIKKNLLGTLLFDEGNTA--ENRRLKRTARRRYT
73


WP_044676715
1
MKKK-YAIGIDIGTNSVGWSVVTDDYKVPSKKMKVFGNTEKRYIKKNLLGTLLFDEGNTA--ENRRLKRTARRRYT
73


WP_044680361
1
MKKK-YAIGIDIGTNSVGWSVVTDDYKVPSKKMKVFGNTEKRYIKKNLLGTLLFDEGNTA--ENRRLKRTARRRYT
73


WP_044681799
1
MKKK-YAIGIDIGTNSVGWSVVTDDYKVPSKKMKVFGNTEKRYIKKNLLGTLLFDEGNTA--ENRRLKRTARRRYT
73


WP_049533112
1
MDQK-YSIGLDIGTNSVGWAVVTDDYKVPAKKMKVLGNTDKQSIKKNLLGALLFDSGETA--EATRLKRTARRRYT
73


WP_029090905
1
-----------------------------------------------MWGVSLFEAGKTA--AERRGYRSTRRRLN
27


WP_006506696
1
I-VD-YCIGLDLGTGSVGWAVVDMNHRLMKRN------------GKHLWGSRLFSNAETA--ANRRASRSIRRRYN
60


AIT42264
1
MDKK-YSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_034440723
1
-MKN-YTIGLDIGTNSVGWAVIKDDLTLVRKKIKISGNTDKKEVKKNLWGSFLFEQGDTA--QDTRVKRIARRRYE
72


AKQ21048
1
MDKK-YSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


WP_004636532
1
MQKN-YTIGLDIGTNSVGWAVMKDDYTLIRKRMKVLGNTDIKKIKKNFWGVRLFDEGETA--KETRLKRGTRRRYQ
73


WP_002364836
1
MKKD-YVIGLDIGTNSVGWAVMTEDYQLVKKKMPIYGNTEKKKIKKNFWGVRLFEEGHTA--EDRRLKRTARRRIS
73


WP_016631044
1
--------------------------------------------------MRLFEEGHTA--EDRRLKRTARRRIS
24


EMS75795

----------------------------------------------------------------------------



WP_002373311
1
MKKD-YVIGLDIGTNSVGWAVMTEDYQLVKKKMPIYGNTEKKKIKKNFWGVRLFEEGHTA--EDRRLKRTARRRIS
73


WP_002378009
1
MKKD-YVIGLDIGTNSVGWAVMTEDYQLVKKKMPIYGNTEKKKIKKNFWGVRLFEEGHTA--EDRRLKRTARRRIS
73


WP_002407324
1
MKKD-YVIGLDIGTNSVGWAVMTEDYQLVKKKMPIYGNTEKKKIKKNFWGVRLFEEGHTA--EDRRLKRTARRRIS
73


WP_002413717
1
MKKD-YVIGLDIGTNSVGWAVMTEDYQLVKKKMPIYGNTEKKKIKKNFWGVRLFEEGHTA--EDRRLKRTARRRIS
73


WP_010775580
1
MKKD-YVIGLDIGTNSVGWAVMTEDYQLVKKKMPIYGNTEKKKIKKNFWGVRLFEEGHTA--EDRRLKRTARRRIS
73


WP_010818269
1
MKKD-YVIGLDIGTNSVGWAVMTEDYQLVKKKMPIYGNTEKKKIKKNFWGVRLFEEGHTA--EDRRLKRTARRRIS
73


WP_010824395
1
MKKD-YVIGLDIGSNSVGWAVMTEDYQLVKKKMPIYGNTEKKKIKKNFWGVRLFEEGHTA--EDRRLKRTARRRIS
73


WP_016622645
1
MKKD-YVIGLDIGTNSVGWAVMTEDYQLVKKKMPIYGNTEKKKIKKNFWGVRLFEEGHTA--EDRRLKRTARRRIS
73


WP_033624816
1
MKKD-YVIGLDIGTNSVGWAVMTEDYQLVKKKMPIYGNTEKKKIKKNFWGVRLFEEGHTA--EDRRLKRTARRRIS
73


WP_033625576
1
MKKD-YVIGLDIGTNSVGWAVMTEDYQLVKKKMPIYGNTEKKKIKKNFWGVRLFEEGHTA--EDRRLKRTARRRIS
73


WP_033789179
1
MKKD-YVIGLDIGTNSVGWAVMTEDYQLVKKKMPIYGNTEKKKIKKNFWGVRLFEEGHTA--EDRRLKRTARRRIS
73


WP_002310644
1
MKKE-YTIGLDIGTNSVGWSVLTDDYRLVSKKMKVAGNTEKSSTKKNFWGVRLFDEGQTA--EARRSKRTARRRLA
73


WP_002312694
1
MKKE-YTIGLDIGTNSVGWSVLTDDYRLVSKKMKVAGNTEKSSTKKNFWGVRLFDEGQTA--EARRSKRTARRRLA
73


WP_002314015
1
MKKE-YTIGLDIGTNSVGWSVLTDDYRLVSKKMKVAGNTEKSSTKKNFWGVRLFDEGQTA--EARRSKRTARRRLA
73


WP_002320716
1
MKKE-YTIGLDIGTNSVGWSVLTDDYRLVSKKMKVAGNTEKSSTKKNFWGVRLFDEGQTA--EARRSKRTARRRLA
73


WP_002330729
1
MKKE-YTIGLDIGTNSVGWSVLTDDYRLVSKKMKVAGNTEKSSTKKNFWGVRLFDEGQTA--EARRSKRTARRRLA
73


WP_002335161
1
MKKE-YTIGLDIGTNSVGWSVLTDDYRLVSKKMKVAGNTEKSSTKKNFWGVRLFDEGQTA--EARRSKRTARRRLA
73


WP_002345439
1
MKKE-YTIGLDIGTNSVGWSVLTDDYRLVSKKMKVAGNTEKSSTKKNFWGVRLFDEGQTA--EARRSKRTARRRLA
73


WP_034867970
1
MTKD-YTIGLDIGTNSVGWAVLTDDYQLMKRKMSVHGNTEKKKIKKNFWGARLFDEGQTA--EFRRTKRTNRRRLA
73


WP_047937432
1
MKKE-YTIGLDIGTNSVGWSVLTDDYRLVSKKMKVAGNTEKSSTKKNFWGVRLFDEGQTA--EARRSKRTARRRLA
73


WP_010720994
1
MTKD-YTIGLDIGTNSVGWAVLTDDYQLMKRKMSVHGNTEKKKIKKNFWGARLFDEGQTA--EFRRTKRTNRRRLA
73


WP_010737004
1
MTKD-YTIGLDIGTNSVGWAVLTDDYQLMKRKMSVHGNTEKKKIKKNFWGARLFDEGQTA--EFRRTKRTNRRRLA
73


WP_034700478
1
MTKD-YTIGLDIGTNSVGWAVLTDDYQLMKRKMSVHGNTEKKKIKKNFWGARLFDEGQTA--EFRRTKRTNRRRLA
73


WP_007209003
1
MKND-YTIGLDIGTNSVGYSVVTDDYKVISKKMNVFGNTEKKSIKKNFWGVRLFESGQTA--QEARMKRTSRRRIA
73


WP_023519017
1
MEKE-YTIGLDIGTNSVGWAVLTDDYRLVARKMSIQGDSNRKKIKKNFWGARLFEEGKTA--QFRRIKRTNRRRIA
73


WP_010770040
1
MKKE-YTIGLDIGTNSVGWAVLTENYDLVKKKMKVYGNTETKYLKKNLWGVRLFDEGETA--ADRRLKRTTRRRYS
73


WP_048604708
1
MGKE-YTIGLDIGTNSVGWAVLQEDLDLVRRKMKVYGNTEKNYLKKNFWGVDLFDEGMTA--KDTRLKRTTRRRYF
73


WP_010750235
1
MNKA-YTLGLDIGTNSVGWAVVTDDYRLMAKKMPVHSKMEKKKIKKNFWGARLFDEGQTA--EERRNKRATRRRLR
73


AII16583
1
ADKK-YSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
112


WP_029073316
1
NNKI-YNIGLDIGDASVGWAVVDEHYNLLKRH------------GKHMWGSRLFTQANTA--VERRSSRSTRRRYN
65


WP_031589969
1
NNKI-YNIGLDIGDASVGWAVVDEHYNLLKRH------------GKHMWGSRLFTQANTA--VERRSSRSTRRRYN
65


KDA45870
1
LKKD-YSIGLDIGTNSVGHAVVTDDYKVPTKKMKVFGDTSKKTIKKNMLGVLLFNEGQTA--ADTRLKRGARRRYT
74


WP_039099354
1
MSRP-YNIGLDIGTSSIGWSVVDDQSKLVSVR------------GKYGYGVRLYDEGQTA--AERRSFRTTRRRLK
61


AKP02966
1
KEQP-YNIGLDIGTGSVGWAVTNDNYDLLNIK------------KKNLWGVRLFEGAQTA--KETRLNRSTRRRYR
64


WP_010991369
1
MKKP-YTIGLDIGTNSVGWAVLTDQYDLVKRKMKIAGDSEKKQIKKNFWGVRLFDEGQTA--ADRRMARTARRRIE
73


WP_033838504
1
MKKP-YTIGLDIGTNSVGWAVLTDQYDLVKRKMKIAGDSEKKQIKKNFWGVRLFDEGQTA--ADRRMARTARRRIE
73


EHN60060
1
MKKP-YTIGLDIGTNSVGWAVLTDQYDLVKRKMKIAGDSEKKQIKKNFWGVRLFDEGQTA--ADRRMARTARRRIE
76


EFR89594

----------------------------------------------------------------------------



WP_038409211
1
MRKP-YTIGLDIGTNSVGWAVLTDQYNLVKRKMKVAGSAEKKQIKKNFWGVRLFDEGEVA--AGRRMNRTTRRRIE
73


EFR95520

----------------------------------------------------------------------------



WP_003723650
1
MKNP-YTIGLDIGTNSVGWAVLTNQYDLVKRKMKVAGNSDKKQIKKNFWGVRLFDDGQTA--VDRRMNRTARRRIE
73


WP_003727705
1
MKNP-YTIGLDIGTNSVGWAVLTDQYDLVKRKMKVAGNSDKKQIKKNFWGVRLFDDGQTA--VDRRMNRTARRRIE
73


WP_003730785
1
MKNP-YTIGLDIGTNSVGWAVLTDQYDLVKRKMKVAGNSDKKQIKKNFWGVRLFDDGQTA--VDRRMNRTARRRIE
73


WP_003733029
1
MKKP-YTIGLDIGTNSVGWAVLTDQYDLVKRKMKISGDSEKKQIKKNFWGVRLFEKGETA--AKRRMSRTARRRIE
73


WP_003739838
1
MKNP-YTIGLDIGTNSVGWAVLTDQYDLVKRKMKVAGNSDKKQIKKNFWGVRLFDEGETA--ADRRMNRTARRRIE
73


WP_014601172
1
MKNP-YTIGLDIGTNSVGWAVLTNQYDLVKRKMKVAGNSDKKQIKKNFWGVRLFDDGQTA--VDRRMNRTARRRIE
73


WP_023548323
1
MKNP-YTIGLDIGTNSVGWAVLTNQYDLVKRKMKVAGNSDKKQIKKNFWGVRLFDDGQTA--VDRRMNRTARRRIE
73


WP_031665337
1
MKNP-YTIGLDIGTNSVGWAVLTDQYDLVKRKMKVAGNSDKKQIKKNFWGVRLFDDGQTA--VDRRMNRTARRRIE
73


WP_031669209
1
MKKP-YTIGLDIGTNSVGWAVLTDQYDLVKRKMKISGDSEKKQIKKNFWGVRLFEKGETA--AKRRMSRTARRRIE
73


WP_033920898
1
MKNP-YTIGLDIGTNSVGWAVLTNQYDLVKRKMKVAGNSDKKQIKKNFWGVRLFDDGQTA--VDRRMNRTARRRIE
73


AKI42028
1
MKNP-YTIGLDIGTNSVGWAVLTNQYDLVKRKMKVAGNSDKKQIKKNFWGVRLFDDGQTA--VDRRMNRTARRRIE
76


AKI50529
1
MKNP-YTIGLDIGTNSVGWAVLTNQYDLVKRKMKVAGNSDKKQIKKNFWGVRLFDDGQTA--VDRRMNRTARRRIE
76


EFR83390

----------------------------------------------------------------------------



WP_046323366
1
MKKP-YTIGLDIGTNSVGWAALTDQYDLVKRKMKVAGNSEKKQIKKNLWGVRLVDEGKTA--AHRRVNRTTRRRIE
73


AKE81011
1
ADKK-YSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
89


CUO82355
1
I-VD-YCIGLDLGTGSVGWAVVDMNHRLMKRN------------GKHLWGSRLFSNAETA--ATRRSSRSIRRRYN
64


WP_033162887
1
KDIR-YSIGLDIGTNSVGWAVMDEHYELLKKG------------NHHMWGSRLFDAAEPA--ATRRASRSIRRRYN
65


AGZ01981
1
ADKK-YSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
106


AKA60242
1
MDKK-YSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


AKS40380
1
MDKK-YSIGLDIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
73


4UN5_B
1
MDKK-YSIGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSGETA--EATRLKRTARRRYT
77


WP_010922251
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNcustom character V-DEVAYHEKYPTIYcustom character LRKKLV
143


WP_039695303
75
RRKNRLRYLQEIFANEIAKVDESFFQRLDE-SFLT--DDDKT---F DSHPIFGNKA-EEDAYHQKFPTIYHLRKHLA
144


WP_045635197
74
RRKNRLRYLQEIFSEEMSKVDSSFFHRLDD-SFLI--PEDKR---E SKYPIFATLT-EEKEYHKQFPTIYHLRKQLA
143


5AXW_A
62
RRRHRIQRVKKLLFD---------YNLLTDhSELS----------G --NPYEARVK--------------GLSQKLS
104


WP_009880683

---------------------------------------------- -------------------------------



WP_010922251
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLV
143


WP_011054416
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


WP_011284745
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLV
143


WP_011285506
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLV
143


WP_011527619
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLV
143


WP_012560673
74
RRKNRICYLQEIFSNEIAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


WP_014407541
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


WP_020905136
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLV
143


WP_023080005
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


WP_023610282
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


WP_030125963
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLV
143


WP_030126706
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


WP_031488318
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


WP_032460140
74
RRKNRICYLQEIFSNEIAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


WP_032461047
74
RRKNRICYLQEIFSNEIAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


WP_032462016
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLV
143


WP_032462936
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


WP_032464890
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLV
143


WP_033888930

---------------------------------------------- -------------------------------



WP_038431314
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


WP_038432938
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


WP_038434062
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


BAQ51233
1
----------------MAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLV
54


KGE60162

---------------------------------------------- -------------------------------



KGE60856

---------------------------------------------- -------------------------------



WP_002989955
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLV
143


WP_003030002
74
RRRNRLRYLQEIFAEEMNKVDENFFQRLDD-SFLV--DEDKR---G ERHPIFGNIA-AEVKYHDDFPTIYHLRKHLA
143


WP_003065552
75
RRKNRLRYLQEIFAEEMTKVDESFFQRLDE-SFLRwdDDNKK---L GRYPIFGNKA-DVVKYHQEFPTIYHLRKHLA
146


WP_001040076
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKYYHEKFPTIYHLRKELA
143


WP_001040078
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFPTIYHLRKELA
143


WP_001040080
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


WP_001040081
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


WP_001040083
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


WP_001040085
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


WP_001040087
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


WP_001040088
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


WP_001040089
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


WP_001040090
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


WP_001040091
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


WP_001040092
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATMQ-EEKDYHEKFPTIYHLRKELA
143


WP_001040094
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATMQ-EEKYYHEKFPTIYHLRKELA
143


WP_001040095
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATMQ-EEKYYHEKFPTIYHLRKELA
143


WP_001040096
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATMQ-EEKYYHEKFPTIYHLRKELA
143


WP_001040097
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATMQ-EEKYYHEKFPTIYHLRKELA
143


WP_001040098
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATMQ-EEKYYHEKFPTIYHLRKELA
143


WP_001040099
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATMQ-EEKYYHEKFPTIYHLRKELA
143


WP_001040100
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATMQ-EEKYYHEKFPTIYHLRKELA
143


WP_001040104
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYXIFATLQ-EEKDYHEKFSTIYHLRKELA
143


WP_001040105
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


WP_001040106
74
CRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EDDKR---G SKYPIFATMQ-EEKDYHEKFPTIYHLRKELA
143


WP_001040107
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EDDKR---G SKYPIFATMQ-EEKDYHEKFPTIYHLRKELA
143


WP_001040108
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EDDKR---G SKYPIFATMQ-EEKDYHEKFPTIYHLRKELA
143


WP_001040109
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EDDKR---G SKYPIFATMQ-EEKDYHEKFPTIYHLRKELA
143


WP_001040110
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EDDKR---G SKYPIFATMQ-EEKDYHEKFPTIYHLRKELA
143


WP_015058523
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATMQ-EEKDYHEKFPTIYHLRKELA
143


WP_017643650
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATMQ-EEKYYHEKFPTIYHLRKELA
143


WP_017647151
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EDDKR---G SKYPIFATMQ-EEKDYHEKFPTIYHLRKELA
143


WP_017648376
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EDDKR---G SKYPIFATMQ-EEKDYHEKFPTIYHLRKELA
143


WP_017649527
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFPTIYHLRKELA
143


WP_017771611
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EDDKR---G SKYPIFATMQ-EEKDYHEKFPTIYHLRKELA
143


WP_017771984
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


CFQ25032
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


CFV16040
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


KLJ37842
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


KLJ72361
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


KLL20707
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


KLL42645
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EDDKR---G SKYPIFATMQ-EEKDYHEKFPTIYHLRKELA
143


WP_047207273
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


WP_047209694
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATMQ-EEKYYHEKFPTIYHLRKELA
143


WP_050198062
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


WP_050201642
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


WP_050204027
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EDDKR---G SKYPIFATMQ-EEKDYHEKFPTIYHLRKELA
143


WP_050881965
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


WP_050886065
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


AHN30376
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATMQ-EEKDYHEKFPTIYHLRKELA
143


EAO78426
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFSTIYHLRKELA
143


CCW42055
74
RRRNRILYLQEIFAEKMSKVDDSFFHRLED-SFLV--EEDKR---G SKYPIFATLQ-EEKDYHEKFPTIYHLRKELA
143


WP_003041502
74
RRRNRLRYLQEIFAEEMMQVDESFFQRLDD-SFLV--DEDKR---G ERHPIFGNIA-AEVKYHDEFPTIYHLRKHLA
143


WP_037593752
75
RRKNRLRYLQEIFTEEMNKVDENFFQRLDD-SFLV--EEDKQ---G SKYPIFGTLK-EEKEYHKKFKTIYHLREELA
144


WP_049516684
75
RRRNRLRYLQEIFAEEMMQVDESFFQRLDD-SFLV--EEDKR---G SRYPIFGNIA-AEVKYHDDFPTIYHLRKHLV
144


GAD46167
74
RRKNRLRYLQEIFTEEMNKVDENFFQRLDD-SFLV--EEDKQ---G SKYPIFGTLK-EEKEYHKKFKTIYHLREELA
143


WP_018363470
75
RRKNRLRYLQDIFTEEMAKVDDSFFQRLDE-SFLT--DNDKN---F DSHPIFGNKA-EEDAYHQKFPTIYHLRKHLA
144


WP_003043819
74
RRKNRIRYLQEIFANEMAKLDDSFFQRLEE-SFLV--EEDKK---N ERHPIFGNLA-DEVAYHRNYPTIYHLRKKLA
143


WP_006269658
74
RRKNRLRYLQEIFTGEMNKVDENFFQRLDD-SFLV--DEDKR---G EHHPIFGNIA-AEVKYHDDFPTIYHLRRHLA
143


WP_048800889
74
RRKNRLRYLQEIFIEEMNKVDENFFQRLDD-SFLV--TEDKR---G SKYPIFGTLK-EEKEYYKEFETIYHLRKRLA
143


WP_012767106
74
RRKNRIRYLQEIFSSEMSKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


WP_014612333
74
RRKNRIRYLQEIFSSEMSKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


WP_015017095
74
RRKNRIRYLQEIFSSEMSKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


WP_015057649
74
RRKNRIRYLQEIFSSEMSKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


WP_048327215
74
RRKNRIRYLQEIFSSEMSKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


WP_049519324
74
RRKNRIRYLQEIFSSEMSKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLA
143


WP_012515931
74
RRKNRLRYLKEIFTEEMAKVDDGFFQRLED-SFYV--LEDKE---G NKHPIFANLA-DEVAYHKKYPTIYHLRKELV
143


WP_021320964
74
RRKNRLRYLKEIFTEEMAKVDDGFFQRLED-SFYV--LEDKE---G NKHPIFANLA-DEVAYHKKYPTIYHLRKELV
143


WP_037581760
74
RRKNRLRFLKEIFTEEMAKVDDGFFQRLED-SFYV--LEDKE---G NKHPIFANLA-DEVAYHKKYPTIYHLRKELV
143


WP_004232481
74
RRKNRLRYLQEIFAKEMAKVDESFFQRLEE-SFLT--DDDKT---F DSHPIFGNKA-EEDTYHQEFPTIYHLRKHLA
143


WP_009854540
75
RRKNRLRYLQEIFAEEMTKVDESFFYRLDE-SFLT--TDEKD---F ERHPIFGNKA-EEDAYHQKFPTIYHLRNYLA
144


WP_012962174
75
RRKNRLRYLQEIFAEEMAKVDESFFYRLDE-SFLT--TDDKD---F ERHPIFGNKA-DEIKYHQEFPTIYHLRKHLA
144


WP_039695303
75
RRKNRLRYLQEIFANEIAKVDESFFQRLDE-SFLT--DDDKT---F DSHPIFGNKA-EEDAYHQKFPTIYHLRKHLA
144


WP_014334983
74
RRKNRLRYLQEIFAKEMTKVDESFFQRLEE-SFLT--DDDKT---F DSHPIFGNKA-EEDAYHQKFPTIYHLRKYLA
143


WP_003099269
74
RRKYRIKELQKIFSSEMNELDIAFFPRLSE-SFLV--SDDKE---F ENHPIFGNLK-DEITYHNDYPTIYHLRQTLA
143


AHY15608
74
RRKYRIKELQKIFSSEMNELDIAFFPRLSE-SFLV--SDDKE---F ENHPIFGNLK-DEITYHNDYPTIYHLRQTLA
143


AHY17476
74
RRKYRIKELQKIFSSEMNELDIAFFPRLSE-SFLV--SDDKE---F ENHPIFGNLK-DEITYHNDYPTIYHLRQTLA
143


ESR09100

---------------------------------------------- -------------------------------



AGM98575
74
RRKYRIKELQKIFSSEMNELDIAFFPRLSE-SFLV--SDDKE---F ENHPIFGNLK-DEITYHNDYPTIYHLRQTLA
143


ALF27331
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_018372492
74
RRRNRIRYLQHIFAEEMNRADENFFHRLKE-SFFV--EEDKT---Y SKYPIFGTLE-EEKNYHKNYPTIYHLRKTLA
143


WP_045618028
75
RRKNRLRYLQEIFTEEMSKVDISFFHRLDD-SFLV--PEDKR---G SKYPIFATLE-EEKEYHKNFPTIYHLRKHLA
144


WP_045635197
74
RRKNRLRYLQEIFSEEMSKVDSSFFHRLDD-SFLI--PEDKR---E SKYPIFATLT-EEKEYHKQFPTIYHLRKQLA
143


WP_002263549
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002263887
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002264920
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLDE-SFLT--DDDKN---F DSYPIFGNKA-EEDAYHQKFPTIYHLRKHLA
143


WP_002269043
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002269448
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002271977
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002272766
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002273241
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002275430
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002276448
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002277050
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLDE-SFLT--DDDKN---F DSHPIFGNKA-EEDAYHQKFPTIYHLRKHLA
143


WP_002277364
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002279025
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-FFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002279859
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLDE-SFLT--DDDKN---F DSHPIFGNKA-EEDAYHQKFPTIYHLRKHLA
143


WP_002280230
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002281696
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002282247
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLDE-SFLT--DDDKN---F DSHPIFGNKA-EEDAYHQKFPTIYHLRKHLA
143


WP_002282906
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002283846
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002287255
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002288990
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002289641
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002290427
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002295753
74
RRRNRILYLQEIFSEEMGKVNDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002296423
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002304487
74
RRRNRILYLQEIFAEEMMQVDESFFQRLDD-SFLV--EEDKR---G SRYPIFGTLK-EEKKYHKEFKTIYHLREKLA
143


WP_002305844
74
RRRNRILYLQEIFSEEMDKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002307203
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002310390
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_002352408
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_012997688
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_014677909
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_019312892
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_019313659
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_019314093
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_019315370
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ECHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_019803776
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_019805234
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_024783594
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_024784288
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLDE-SFLT--DDDKN---F DSHPIFGNKA-EEDAYHQKFPTIYHLRKHLA
143


WP_024784666
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_024784894
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


WP_024786433
74
RRRNRILYLQEIFAEEMNKVDDSFFHRLDE-SFLT--DDDKN---F DSHPIFGNKA-EEDAYHQKFPTIYHLRKHLA
143


WP_049473442
74
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYYENFPTIYHLRQYLA
143


WP_049474547
74
RRRNRILYLQEIFSEEMGKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
143


EMC03581
67
RRRNRILYLQEIFAEEMSKVDDSFFHRLED-SFLV--TEDKR---G ERHPIFGNLE-EEVKYHENFPTIYHLRQYLA
136


WP_000428612
75
RRKNRLRYLQEIFAEEMSKVDSSFFHRLDD-SFLI--PEDKK---G SKYPIFATLI-EEKEYHKQFPTIYHLRKQLA
144


WP_000428613
75
RRKNRLRYLQEIFAEEMSKVDSSFFHRLDD-SFLI--PEDKR---G SKYPIFATLA-EEKEYHKQFPTIYHLRKQLA
144


WP_049523028
74
RRRNRILYLQEIFAAEMNKVDESFFHRLDD-SFLV--PEDKR---G SKYPIFGTLE-EEKEYHKQFPTIYYLRKILA
143


WP_003107102
43
RRINRIKYLQSIFDDEMSKIDSAFFQRIKD-SFLV--PDDKN---D DRHPIFGNIK-DEVDYHKNYPTIYHLRKKLA
112


WP_054279288
76
RRKNRLCYLRDIFESEMHTIDKHFFLRLED-SFLH--KSDKR---Y EAHPIFGTLQ-EEKAYHDNYPTIYHLRKALA
145


WP_049531101
75
RRKNRLRYLQEIFSEEISKVDNSFFHRLDD-SFLV--PEDKR---G SKYPIFATLT-EEKEYYKQFPTIYHLRKQLA
144


WP_049538452
75
RRKNRLRYLQEIFAEEMNKVDSSFFHRLDD-SFLV--PEDKR---G SKYPIFATLA-EEKEYHKNFPTIYHLRKQLA
144


WP_049549711
75
RRKNRLRYLQEIFSGEMSKVDSSFFHRLDD-SFLV--PEDKR---G SKYPIFATLV-EEKEYHKQFPTIYHLRKQLA
144


WP_007896501
76
RRRYRLCQLQNIFATEMVKVDDTFFQRLSE-SFFY--YQDKA---F DKHPIFGNSK-EERAYHKTYPTIYHLRKDLA
145


EFR44625
28
RRRYRLCQLQNIFATEMVKVDDTFFQRLSE-SFFY--YQDKA---F DKHPIFGNSK-EERAYHKTYPTIYHLRKDLA
97


WP_002897477
74
RRRNRILYLQEIFTESMNEIDESFFHRLDD-SFLV--PEDKR---G SKYPIFATLQ-EEKEYHKQFPTIYHLRKQLA
143


WP_002906454
74
RRKNRLRYLQEIFSEEISKLDSSFFHRLDD-SFLV--PEDKR---G SKYPIFATLE-EEKEYHKKFPTIYHLRKHLA
143


WP_009729476
75
RRKNRLRYLQEIFSEEIGKVDSSFFHRLDD-SFLI--PEDKR---G SKYPIFATLA-EEKKYHKQFPTIYHLRKQLA
144


CQR24647
74
RRRNRILYLQDIFSPELNQVDESFLHRLDD-SFLVa--EDKR---G ERHVIFGNIA-DEVKYHKEFPTIYHLRKHLA
143


WP_000066813
75
RRKNRLRYLQEIFSQEISKVDSSFFHRLDD-FFLV--PEDKR---G SKYPIFATLV-EEKEYHKKFPTIYHLRKHLA
144


WP_009754323
75
RRKNRLRYLQEIFAEEMSKVDSSFFHRLDD-SFLV--PEDKS---G SKYPIFATLA-EEKEYHKKFPTIYHLRKHLA
144


WP_044674937
74
RRRNRILYLQEIFAEEINKIDDSFFQRLDD-SFLIv--EDKQ---G SKHPIFGTLQ-EEKKYHKQFPTIYHLRKQLA
143


WP_044676715
74
RRRNRILYLQEIFAEEINKIDDSFFQRLDD-SFLIv--EDKQ---G SKHPIFGTLQ-EEKEYHKQFPTIYHLRKQLA
143


WP_044680361
74
RRRNRILYLQEIFAEEINKIDDSFFQRLDD-SFLIv--EDKQ---G SKHPIFGTLQ-EEKEYHKQFPTIYHLRKQLA
143


WP_044681799
74
RRRNRILYLQEIFAEEINKIDDSFFQRLDD-SFLIv--EDKQ---G SKHPIFGTLQ-EEKKYHKQFPTIYHLRKQLA
143


WP_049533112
74
RRRNRLRYLQEIFAEEMNKVDENFFQRLDD-SFLV--DEDKR---G ERHPIFGNIA-AEVKYHDDFPTIYHLRKHLA
143


WP_029090905
28
HRKFRLRLLEDMFEKEILSKDPSFFIRLKE-AFLSpkDEQKQ---F ----LFNDKDyTDADYYEQYKTIYHLRYDLI
100


WP_006506696
61
KRRERIRLLRAILQDMVLEKDPTFFIRLEHtSFLD--EEDKAkylG DNYNLFIDEDfNDYTYYHKYPTIYHLRKALC
139


AIT42264
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLV
143


WP_034440723
73
RRRFRIRELQKIFDKSMGEVDSNFFHRLDE-SFLV--EEDKE---Y SKYPIFSNEK-EDKNYYDKYPTIYHLRKDLA
142


AKQ21048
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLV
143


WP_004636532
74
RRRNRLIYLQDIFQQPMLAIDENFFHRLDD-SFFV--PDDKS---Y DRHPIFGSLE-EEVAYHNTYPTIYHLRKHLA
143


WP_002364836
74
RRRNRLRYLQAFFEEAMTDLDENFFARLQE-SFLV--PEDKK---W HRHPIFAKLE-DEVAYHETYPTIYHLRKKLA
143


WP_016631044
25
RRRNRLRYLQAFFEEAMTDLDENFFARLQE-SFLV--PEDKK---W HRHPIFAKLE-DEVAYHETYPTIYHLRKKLA
94


EMS75795

---------------------------------------------- -------------------------------



WP_002373311
74
RRRNRLRYLQAFFEEAMTDLDENFFARLQE-SFLV--PEDKK---W HRHPIFAKLE-DEVAYHETYPTIYHLRKKLA
143


WP_002378009
74
RRRNRLRYLQAFFEEAMTALDENFFARLQE-SFLV--PEDKK---W HRHPIFAKLE-DEVAYHETYPTIYHLRKKLA
143


WP_002407324
74
RRRNRLRYLQAFFEEAMTALDENFFARLQE-SFLV--PEDKK---W HRHPIFAKLE-DEVAYHETYPTIYHLRKKLA
143


WP_002413717
74
RRRNRLRYLQAFFEEAMTDLDENFFARLQE-SFLV--PEDKK---W HRHPIFAKLE-DEVAYHETYPTIYHLRKKLA
143


WP_010775580
74
RRRNRLRYLQAFFEEAMTALDENFFARLQE-SFLV--PEDKK---W HRHPIFAKLE-DEVAYHETYPTIYHLRKKLA
143


WP_010818269
74
RRRNRLRYLQAFFEEAMTALDENFFARLQE-SFLV--PEDKK---W HRHPIFAKLE-DEVAYHETYPTIYHLRKKLA
143


WP_010824395
74
RRRNRLRYLQAFFEEAMTDLDENFFARLQE-SFLV--PEDKK---W HRHPIFAKLE-DEVAYHETYPTIYHLRKKLA
143


WP_016622645
74
RRRNRLRYLQAFFEEAMTALDENFFARLQE-SFLV--PEDKK---W HRHPIFAKLE-DEVAYHETYPTIYHLRKKLA
143


WP_033624816
74
RRRNRLRYLQAFFEEAMTALDENFFARLQE-SFLV--PEDKK---W HRHPIFAKLE-DEVAYHETYPTIYHLRKKLA
143


WP_033625576
74
RRRNRLRYLQAFFEEAMTALDENFFARLQE-SFLV--PEDKK---W HRHPIFAKLE-DEVAYHETYPTIYHLRKKLA
143


WP_033789179
74
RRRNRLRYLQAFFEEAMTALDENFFARLQE-SFLV--PEDKK---W HRHPIFAKLE-DEVAYHETYPTIYHLRKKLA
143


WP_002310644
74
RRRQRILELQKIFAPEILKIDEHFFARLNE-SFLV--LDEKK---Q SRHPVFATIK-QEKSYHQTYPTIYHLRQALA
143


WP_002312694
74
RRRQRILELQKIFAPEILKIDEHFFARLNE-SFLV--PDEKK---Q SRHPVFATIK-QEKSYHQTYPTIYHLRQALA
143


WP_002314015
74
RRRQRILELQKIFAPEILKIDEHFFARLNE-SFLV--LDEKK---Q SRHPVFATIK-QEKSYHQTYPTIYHLRQALA
143


WP_002320716
74
RRRQRILELQKIFAPEILKIDEHFFARLNE-SFLV--LDEKK---Q SRHPVFATIK-QEKSYHQTYPTIYHLRQALA
143


WP_002330729
74
RRRQRILELQKIFAPEILKIDEHFFARLNE-SFLV--LDEKK---Q SRHPVFATIK-QEKSYHQTYPTIYHLRQALA
143


WP_002335161
74
RRRQRILELQKIFAPEILKIDEHFFARLNE-SFLV--LDEKK---Q SRHPVFATIK-QEKSYHQTYPTIYHLRQALA
143


WP_002345439
74
RRRQRILELQKIFAPEILKIDEHFFARLNE-SFLV--LDEKK---Q SRHPVFATIK-QEKSYHQTYPTIYHLRQALA
143


WP_034867970
74
RRKYRLSKLQDLFAEELCKQDDCFFVRLEE-SFLV--PEEKQ---Y KPASIFPTLE-EEKEYYQKYPTIYHLRQKLV
143


WP_047937432
74
RRRQRILELQKIFAPEILKIDEHFFARLNE-SFLV--LDEKK---Q SRHPVFATIK-QEKSYHQTYPTIYHLRQALA
143


WP_010720994
74
RRKYRLSKLQDLFAEELCKQDDCFFVRLEE-SFLV--PEEKQ---Y KPASIFPTLE-EEKEYYQKYPTIYHLRQKLV
143


WP_010737004
74
RRKYRLSKLQDLFAEELCKQDDCFFVRLEE-SFLV--PEEKQ---Y KPASIFPTLE-EEKEYYQKYPTIYHLRQKLV
143


WP_034700478
74
RRKYRLSKLQDLFAEELCKQDDCFFVRLEE-SFLV--PEEKQ---Y KPASIFPTLE-EEKEYYQKYPTIYHLRQKLV
143


WP_007209003
74
RRKNRICYLQEIFQPEMNHLDNNFFYRLNE-SFLVa--DDAK---Y DKHPIFGTLD-EEIHFHEQFPTIYHLRKYLA
143


WP_023519017
74
RRRQRVLALQDIFAEEIHKKDPNFFARLEE-GDRV--EADKR---F AKFPVFATLS-EEKNYHRQYPTIYHLRHDLA
143


WP_010770040
74
RRRNRICRLQDLFTEEMNQVDANFFHRLQE-SFLV--PDEKE---F ERHAIFGKME-EEVSYYREFPTIYHLRKHLA
143


WP_048604708
74
RRRQRISYLQTFFQEEMNRIDPNFFNRLDE-SFLI--EEDKL---S ERHPIFGTIE-EEVAYHKNYATIYHLRKELA
143


WP_010750235
74
RRKYRILELQKIFSEEILKKDSHFFARLDE-SFLI--PEDKQ---Y ARFPIFPTLL-EEKAYYQNYPTIYHLRQKLA
143


AII16583
113
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLV
182


WP_029073316
66
KRRERIRLLRGIMEDMVLDVDPTFFIRLANvSFLD--QEDKKdylK SNYNLFIDKDfNDKTYYDKYPTIYHLRKHLC
144


WP_031589969
66
KRRERIRLLREIMEDMVLDVDPTFFIRLANvSFLD--QEDKKdylK SNYNLFIDKDfNDKTYYDKYPTIYHLRKHLC
144


KDA45870
75
RRKNRLRYLQEIFAPALAKVDPNFFYRLEE-SSLVa--EDKK---Y DVYPIFGKRE-EELLYHDTHKTIYHLRSELA
144


WP_039099354
62
RRKWRLGLLREIFEPYITPVDDTFFLRKKQ-SNLS--PKDQR---K -QTSLFNDRT--DRAFYDDYPTIYHLRYKLM
132


AKP02966
65
RRKNRINWLNEIFSEELANTDPSFLIRLQN-SWVSkkDPDRK---R DKYNLFIDNPyTDKEYYREFPTIFHLRKELI
137


WP_010991369
74
RRRNRISYLQGIFAEEMSKTDANFFCRLSD-SFYV--DNEKR---N SRHPFFATIE-EEVEYHKNYPTIYHLREELV
143


WP_033838504
74
RRRNRISYLQGIFAEEMSKTDANFFCRLSD-SFYV--DNEKR---N SRHPFFATIE-EEVEYHKNYPTIYHLREELV
143


EHN60060
77
RRRNRISYLQGIFAEEMSKTDANFFCRLSD-SFYV--DNEKR---N SRHPFFATIE-EEVEYHKNYPTIYHLREELV
146


EFR89594

---------------------------------------------- -------------------------------



WP_038409211
74
RRRNRIAYLQEIFAAEMAEVDANFFYRLED-SFYI--ESEKR---H SRHPFFATIE-EEVAYHEEYKTIYHLREKLV
143


EFR95520

---------------------------------------------- -------------------------------



WP_003723650
74
RRRNRISYLQEIFAVEMANIDANFFCRLND-SFYV--DSEKR---N SRHPFFATIE-EEVAYHDNYRTIYHLREKLV
143


WP_003727705
74
RRRNRISYLQEIFAVEMANIDANFFCRLND-SFYV--DSEKR---N SRHPFFATIE-EEVAYHKNYRTIYHLREELV
143


WP_003730785
74
RRRNRISYLQEIFAVEMANIDANFFCRLND-SFYV--DSEKR---N SRHPFFATIE-EEVAYHKNYRTIYHLREELV
143


WP_003733029
74
RRRNRISYLQEIFAIQMNEVDDNFFNRLKE-SFYA--ESDKK---Y NRHPFFGTVE-EEVAYYKDFPTIYHLRKELI
143


WP_003739838
74
RRRNRISYLQEIFALEMANIDANFFCRLND-SFYV--DSEKR---N SRHPFFATIE-EEVAYHKNYRTIYHLREELV
143


WP_014601172
74
RRRNRISYLQEIFAVEMANIDANFFCRLND-SFYV--DSEKR---N SRHPFFATIE-EEVAYHKNYRTIYHLREELV
143


WP_023548323
74
RRRNRISYLQEIFAVEMANIDANFFCRLND-SFYV--DSEKR---N SRHPFFATIE-EEVAYHKNYRTIYHLREELV
143


WP_031665337
74
RRRNRISYLQEIFAVEMANIDANFFCRLND-SFYV--DSEKR---N SRHPFFATIE-EEVAYHKNYRTIYHLREELV
143


WP_031669209
74
RRRNRISYLQEIFAIQMNEVDDNFFNRLKE-SFYA--ESDKK---Y NRHPFFGTVE-EEVAYYKDFPTIYHLRKELI
143


WP_033920898
74
RRRNRISYLQEIFAVEMANIDANFFCRLND-SFYV--DSEKR---N SRHPFFATIE-EEVAYHKNYRTIYHLREELV
143


AKI42028
77
RRRNRISYLQEIFAVEMANIDANFFCRLND-SFYV--DSEKR---N SRHPFFATIE-EEVAYHKNYRTIYHLREELV
146


AKI50529
77
RRRNRISYLQEIFAVEMANIDANFFCRLND-SFYV--DSEKR---N SRHPFFATIE-EEVAYHKNYRTIYHLREELV
146


EFR83390

---------------------------------------------- -------------------------------



WP_046323366
74
RRRNRISYLQEIFTAEMFEVDANFFYRLED-SFYI--ESEKR---Q SRHPFFATIE-EEVAYHENYRTIYHLREKLV
143


AKE81011
90
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLV
159


CUO82355
65
KRRERIRLLRAILQDMVLEKDPTFFIRLEHtSFLD--EEDKAkylG DNYNLFIDEDfNDYTYYHKYPTIYHLRKALC
143


WP_033162887
66
KRRERIRLLRDLLGDMVMEVDPTFFIRLLNvSFLD--EEDKQkn1G DNYNLFIEKDfNDKTYYDKYPTIYHLRKELC
144


AGZ01981
107
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLV
176


AKA60242
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLV
143


AKS40380
74
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLV
143


4UN5_B
78
RRKNRICYLQEIFSNEMAKVDDSFFHRLEE-SFLV--EEDKK---H ERHPIFGNIV-DEVAYHEKYPTIYHLRKKLV
147


WP_010922251
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVcustom character KL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
211


WP_039695303
145
DSSEKADLRLVYLALAHMIKFRGHFLIEGE-LNAENTDVQKI--FADFVGVYNRT--FDDS-H LSEITVDVA---SI
212


WP_045635197
144
DSKEKTDLRLIYLALAHMIKYRGHFLYEEA-FDIKNNDIQKI--FNEFISIYDNT--FEGS-S LSGQNAQVE---AI
211


5AXW_A
105
EEEFSA-------ALLHLAKRRG---VHNV------NEVE------------EDT----GN-- -------E------
134


WP_009880683

--------------------------------------------------------------- --------------



WP_010922251
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
211


WP_011054416
144
DSTDKVDLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASRVDAK---AI
211


WP_011284745
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
211


WP_011285506
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
211


WP_011527619
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
211


WP_012560673
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASRVDAK---AI
211


WP_014407541
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQIYNQL--FEEN-- INASRVDAK---AI
211


WP_020905136
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
211


WP_023080005
144
DSTDKVDLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASRVDAK---AI
211


WP_023610282
144
DSTDKVDLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASRVDAK---AI
211


WP_030125963
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
211


WP_030126706
144
DSTDKVDLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASRVDAK---AI
211


WP_031488318
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASRVDAK---AI
211


WP_032460140
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASRVDAK---AI
211


WP_032461047
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGG-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASRVDAK---AI
211


WP_032462016
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INANGVDAK---AI
211


WP_032462936
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASRVDAK---AI
211


WP_032464890
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
211


WP_033888930
1
---------------------------------PDNSDVDKL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
36


WP_038431314
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASRVDAK---AI
211


WP_038432938
144
DSTDKVDLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASRVDAK---AI
211


WP_038434062
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASRVDAK---AI
211


BAQ51233
55
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
122


KGE60162

--------------------------------------------------------------- --------------



KGE60856

--------------------------------------------------------------- --------------



WP_002989955
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
211


WP_003030002
144
DISQKADLRLVYLALAHMIKFRGHFLIEGQ-LKAENTNVQAL--FKDFVEVYDKT--VEES-H LSEMTVDAL---SI
211


WP_003065552
147
DSSEKADLRLVYLALAHMIKFRGHFLIEGE-LNAENTDVQKI--FADFVGVYDRT--FDDS-H LSEITVDAA---SI
214


WP_001040076
144
DKKEKADLRLVYLALAHIIKFRGHFLIEDDrFDVRNTDIQKQ--YQAFLEIFDTT--FENN-D LLSQDVDVE---AI
212


WP_001040078
144
DKQEKADLRLIYLALAHIIKFRGHFLIEDDrFDVRNTDIQKQ--YQAFLEIFDTT--FENN-H LLSQNVDVE---AI
212


WP_001040080
144
DKKEKADLRLIYIALAHIIKFRGHFLIEDDsFDVRNTDISKQ--YQDFLEIFNIT--FENN-D LLSQNVDVE---AI
212


WP_001040081
144
DKKEKADLRLIYIALAHIIKFRGHFLIEDDsFDVRNTDISKQ--YQDFLEIFNTI--FENN-D LLSQNVDVE---AI
212


WP_001040083
144
DKKEKADLRLIYIALAHIIKFRGHFLIEDDsFDVRNTDISKQ--YQDFLEIFNTT--FENN-D LLSQNVDVE---AI
212


WP_001040085
144
DKKEKADLRLIYIALAHIIKFRGHFLIEDDsFDVRNTDISKQ--YQDFLEIFNTT--FENN-D LLSQNVDVE---AI
212


WP_001040087
144
DKKEKADLRLIYIALAHIIKFRGHFLIEDDsFDVRNTDISKQ--YQDFLEIFNTT--FENN-D LLSQNVDVE---AI
212


WP_001040088
144
DKKEKADLRLIYIALAHIIKFRGHFLIEDDsFDVRNTDISKQ--YQDFLEIFNTT--FENN-D LLSQNVDVE---AI
212


WP_001040089
144
DKKEKADLRLIYIALAHIIKFRGHFLIEDDsFDVRNTDISKQ--YQDFLEIFNTT--FENN-D LLSQNVDVE---AI
212


WP_001040090
144
DKKEKADLRLIYIALAHIIKFRGHFLIEDDsFDVRNTDISKQ--YQDFLEIFNTT--FENN-D LLSQNVDVE---AI
212


WP_001040091
144
DKKEKADLRLIYIALAHIIKFRGHFLIEDDsFDVRNTDISKQ--YQDFLEIFNTT--FENN-D LLSQNVDVE---AI
212


WP_001040092
144
DKKEKADLRLVYLALAHIIKFRGHFLIEDDrFDVRNTDIQKQ--YQAFLEIFDTS--FENN-H LLSQNVDVE---AI
212


WP_001040094
144
DKKEKADLRLIYLALAHIIKFRGHFLIEDDrFDVRNTDIQKQ--YQAFLEIFDTT--FENN-D LLSQNVDVE---AI
212


WP_001040095
144
DKKEKADLRLIYLALAHIIKFRGHFLIEDDrFDVRNTDIQKQ--YQAFLEIFDTT--FENN-D LLSQNVDVE---AI
212


WP_001040096
144
DKKEKADLRLIYLALAHIIKFRGHFLIEDDrFDVRNTDIQKQ--YQAFLEIFDTT--FENN-D LLSQNVDVE---AI
212


WP_001040097
144
DKKEKADLRLIYLALAHIIKFRGHFLIEDDrFDVRNTDIQKQ--YQAFLEIFDTT--FENN-D LLSQNVDVE---AI
212


WP_001040098
144
DKKEKADLRLIYLALAHIIKFRGHFLIEDDrFDVRNTDIQKQ--YQAFLEIFDTT--FENN-D LLSQNVDVE---AI
212


WP_001040099
144
DKKEKADLRLIYLALAHIIKFRGHFLIEDDrFDVRNTDIQKQ--YQAFLEIFDTT--FENN-D LLSQNVDVE---AI
212


WP_001040100
144
DKKEKADLRLIYLALAHIIKFRGHFLIEDDrFDVRNTDIQKQ--YQAFLEIFDTT--FENN-D LLSQNVDVE---AI
212


WP_001040104
144
DKKEKADLRLIYIALAHIIKFRGHFLIEDDsFDVRNTDISKQ--YQDFLEIFNTT--FENN-D LLSQNVDVE---AI
212


WP_001040105
144
DKKEKADLRLIYIALAHIIKFRGHFLIEDDsFDVRNTDISKQ--YQDFLEIFNTT--FENN-D LLSQNVDVE---AI
212


WP_001040106
144
DKKEKANLRLVYLALAHIIKFRGHFLIEDDsFDVRNTDIQRQ--YQAFLEIFDTT--FENN-H LLSQNIDVE---GI
212


WP_001040107
144
DKKEKADLRLVYLALAHIIKFRGHFLIEDDsFDVRNTDIQRQ--YQAFLEIFDTT--FENN-H LLSQNIDVE---GI
212


WP_001040108
144
DKKEKADLRLVYLALAHIIKFRGHFLIEDDsFDVRNTDIQRQ--YQAFLEIFDTT--FENN-H LLSQNIDVE---GI
212


WP_001040109
144
DKKEKANLRLVYLALAHIIKFRGHFLIEDDsFDVRNTDIQRQ--YQAFLEIFDTT--FENN-H LLSQNIDVE---GI
212


WP_001040110
144
DKKEKANLRLVYLALAHIIKFRGHFLIEDDsFDVRNTDIQRQ--YQAFLEIFDTT--FENN-H LLSQNIDVE---GI
212


WP_015058523
144
DKKEKADLRLVYLALAHIIKFRGHFLIEDDrFDVRNTDIQKQ--YQAFLEIFDTS--FENN-H LLSQNVDVE---AI
212


WP_017643650
144
DKKEKADLRLIYLALAHIIKFRGHFLIEDDrFDVRNTDIQKQ--YQAFLEIFDTT--FENN-D LLSQNVDVE---AI
212


WP_017647151
144
DKKEKADLRLFYLALAHIIKFRGHFLIEDDsFDVRNTDIQRQ--YQAFLEIFDTT--FENN-H LLSQNIDIE---GI
212


WP_017648376
144
DKKEKADLRLFYLALAHIIKFRGHFLIEDDsFDVRNTDIQRQ--YQAFLEIFDTT--FENN-H LLSQNIDVE---GI
212


WP_017649527
144
DKKEKADLRLIYIALAHIIKFRGHFLIEDDsFDVRNTDISKQ--YQDFLEIFNTT--FENN-D LLSQNVDVE---AI
212


WP_017771611
144
DKKEKADLRLVYLALAHIIKFRGHFLIEDDsFDVRNTDIQRQ--YQAFLEIFDTT--FENN-H LLSQNIDVE---GI
212


WP_017771984
144
DKKEKADLRLIYIALAHIIKFRGHFLIEDDsFDVRNTDISKQ--YQDFLEIFNTT--FENN-D LLSQNVDVE---AI
212


CFQ25032
144
DKKEKADLRLIYIALAHIIKFRGHFLIEDDsFDVRNTDISKQ--YQDFLEIFNTT--FENN-D LLSQNVDVE---AI
212


CFV16040
144
DKKEKADLRLIYIALAHIIKFRGHFLIEDDsFDVRNTDISKQ--YQDFLEIFNTT--FENN-D LLSQNVDVE---AI
212


KLJ37842
144
DKKEKADLRLIYIALAHIIKERGHFLIEDDsEDVRNTDISKQ--YQDFLEIENTT--FENN-D LLSQNVDVE---AI
212


KLJ72361
144
DKKEKADLRLIYIALAHIIKERGHFLIEDDsEDVRNTDISKQ--YQDFLEIENTT--FENN-D LLSQNVDVE---AI
212


KLL20707
144
DKKEKADLRLIYIALAHIIKERGHFLIEDDsEDVRNTDISKQ--YQDFLEIENTT--FENN-D LLSQNVDVE---AI
212


KLL42645
144
DKKEKANLRLVYLALAHIIKERGHFLIEDDsEDVRNTDIQRQ--YQAFLEIFDTT--FENN-H LLSQNIDVE---GI
212


WP_047207273
144
DKKEKADLRLIYIALAHIIKERGHFLIEDDsEDVRNTDISKQ--YQDFLEIENTT--FENN-D LLSQNVDVE---AI
212


WP_047209694
144
DKKEKADLRLIYLALAHIIKERGHFLIEDDsEDVRNTDIQKQ--YQAFLEIFDTT--FENN-D LLSQNVDVE---AI
212


WP_050198062
144
DKKEKADLRLIYIALAHIIKERGHFLIEDDsEDVRNTDISKQ--YQDFLEIENTT--FENN-D LLSQNVDVE---AI
212


WP_050201642
144
DKKEKADLRLIYIALAHIIKERGHFLIEDDsEDVRNTDISKQ--YQDFLEIENTT--FENN-D LLSQNVDVE---AI
212


WP_050204027
144
DKKEKANLRLVYLALAHIIKERGHFLIEDDsEDVRNTDIQRQ--YQAFLEIFDTT--FENN-H LLSQNIDVE---GI
212


WP_050881965
144
DKKEKADLRLIYIALAHIIKERGHFLIEDDsEDVRNTDISKQ--YQDFLEIENTT--FENN-D LLSQNVDVE---AI
212


WP_050886065
144
DKKEKADLRLIYIALAHIIKERGHFLIEDDsEDVRNTDISKQ--YQDFLEIENTT--FENN-D LLSQNVDVE---AI
212


AHN30376
144
DKKEKADLRLVYLALAHIIKERGHFLIEDDrEDVRNTDIQKQ--YQAFLEIFDTS--FENN-H LLSQNVDVE---AI
212


EA078426
144
DKKEKADLRLIYIALAHIIKERGHFLIEDDsEDVRNTDISKQ--YQDFLEIENTT--FENN-D LLSQNVDVE---AI
212


CCW42055
144
DKKEKADLRLVYLALAHIIKERGHFLIEDDrEDVRNTDIQKQ--YQAFLEIFDTT--FENN-H LLSQNVDVE---AI
212


WP_003041502
144
DISQKADLRLVYLALAHMIKERGHFLIEGQ-LKAENTNVQAL--FKDEVEVYDKT--VEES-H LSEITVDAL---SI
211


WP_037593752
145
NSKEKADLRLVYLALAHMIKERGHFLYEGD-LKAENTDVQAL--FKDEVEEYDKT--IEES-H LSEITVDAL---SI
212


WP_049516684
145
DISQKADLRLVYLALAHMIKERGHFLIEGQ-LKAENTNVQAL--FKDEVEVYDKT--VEES-H LSEMTVDAL---SI
212


GAD46167
144
NSKEKADLRLVYLALAHMIKERGHFLYEGD-LKAENTDVQAL--FKDEVEEYDKT--IEES-H LSEITVDAL---SI
211


WP_018363470
145
DSTEKADLRLVYLALAHMIKERGHFLIEGE-LNAENTDVQKL--FTDEVGVYDRT--FDDS-H LSEITVDAA---SI
212


WP_003043819
144
DSPEKADLRLIYLALAHIIKERGHFLIEGK-LNAENSDVAKL--FYQLIQTYNQL--FEES-- LDEIEVDAK---GI
211


WP_006269658
144
DTSKKADLRLVYLALAHMIKERGHFLYEGD-LKAENTDVQAL--FKDEVEEYDKT--IEES-H LSEITVDAL---SI
211


WP_048800889
144
DSTGKVDLRLVYLALAHMIKERGHFLIEGQ-LKAENTDVQTL--ENDEVEVYDKT--IEES-H LAEITVDAL---SI
211


WP_012767106
144
DSTDKADLRLIYLALAHMIKERGHFLIEGD-LNPDNSDMDKL--FIQLVQTYNQL--FEEN-- INASRVDAK---AI
211


WP_014612333
144
DSTDKADLRLIYLALAHMIKERGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEK-- INASGVDAK---AI
211


WP_015017095
144
DSTDKADLRLIYLALAHMIKERGHFLIEGD-LNPDNSDMDKL--FIQLVQTYNQL--FEEN-- INASRVDAK---AI
211


WP_015057649
144
DSTDKADLRLIYLALAHMIKERGHFLIEGD-LNPDNSDMDKL--FIQLVQTYNQL--FEEN-- INASRVDAK---AI
211


WP_048327215
144
DSTDKADLRLIYLALAHMIKERGHFLIEGD-LNPDNSDMDKL--FIQLVQTYNQL--FEEN-- INASRVDAK---AI
211


WP_049519324
144
DSTDKADLRLIYLALAHMIKERGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASRVDAK---AI
211


WP_012515931
144
DNPQKADLRLIYLAVAHIIKERGHFLIEGT-LSSKNNNLQKS--FDHLVDTYNLL--FEEQ-- LLTEGINAK---EL
211


WP_021320964
144
DNPQKADLRLIYLAVAHIIKERGHFLIEGT-LSSKNNNLQKS--FDHLVDTYNLL--FEEQ-- LLTEGINAK---EL
211


WP_037581760
144
DNPQKADLRLIYLAVAHIIKERGHFLIEGT-LSSKNNNLQKS--FDHLVDTYNLL--FEEQ-- LLTEGINAK---EL
211


WP_004232481
144
DSPEKVDLRLVYLALAHMIKERGHFLIEGQ-LNAENTDVQKI--FADEVGVYDRT--FDDS-H LSEITVDAA---SI
211


WP_009854540
145
DSSEKADLRLVYLALAHMIKYRGHFLIEGK-LNAENTDVQKL--FTDEVGVYDRT--FDDS-H LSEITVDVA---ST
212


WP_012962174
145
DSHEKADLRLIYLALAHMIKERGHFLIEGE-LNAENTDVQKL--FEAFVEVYDRT--FDDS-N LSEITVDAS---SI
212


WP_039695303
145
DSSEKADLRLVYLALAHMIKFRGHFLIEGE-LNAENTDVQKI--FADFVGVYNRT--FDDS-H LSEITVDVA---SI
212


WP_014334983
144
DSQEKADLRLVYLALAHMIKYRGHFLIEGE-LNAENTDVQKL--FNVFVETYDKI--VDES-H LSEIEVDAS---SI
211


WP_003099269
144
DSDQKADLRLIYLALAHIIKFRGHFLIEGN-LDSENTDVHVL--FLNLVNIYNNL--FEED-- VETASIDAE---KI
211


AHY15608
144
DSDQKADLRLIYLALAHIIKFRGHFLIEGN-LDSENTDVHVL--FLNLVNIYNNL--FEED-- VETASIDAE---KI
211


AHY17476
144
DSDQKADLRLIYLALAHIIKFRGHFLIEGN-LDSENTDVHVL--FLNLVNIYNNL--FEED-- VETASIDAE---KI
211


ESR09100

--------------------------------------------------------------- --------------



AGM98575
144
DSDQKADLRLIYLALAHIIKFRGHFLIEGN-LDSENTDVHVL--FLNLVNIYNNL--FEED-- VETASIDAE---KI
211


ALF27331
144
DNPEKTDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---El
211


WP_018372492
144
DTPDKMDIRLIYLALAHIIKYRGHFLIEGD-LDIENIGIQDS--FKSFIEEYNTQ--FGTK-- -LDSTTKVE---Al
209


WP_045618028
145
DSKEKADFRLIYLALAHIIKYRGHFLYEES-FDIKNNDIQKI--FNEFISIYDNT--FEGS-S LNGQNAQVE---AI
212


WP_045635197
144
DSKEKTDLRLIYLALAHMIKYRGHFLYEEA-FDIKNNDIQKI--FNEFISIYDNT--FEGS-S LSGQNAQVE---AI
211


WP_002263549
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002263887
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002264920
144
DSTEKADLRLVYLALAHMIKFRGHFLIEGE-LNAENTDVQKL--FADFVGVYDRT--FDDS-H LSEITVDAS---SI
211


WP_002269043
144
DNPEKTDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002269448
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002271977
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002272766
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002273241
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002275430
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002276448
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002277050
144
DSTEKADLRLVYLALAHMIKFRGHFLIEGE-LNAENTDVQKL--FADFVGVYDRT--FDDS-H LSEITVDAS---SI
211


WP_002277364
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002279025
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002279859
144
DSTEKADLRLVYLALAHMIKFRGHFLIEGE-LNAENTDVQKL--FADFVGVYDRT--FDDS-H LSEITVDAS---SI
211


WP_002280230
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002281696
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002282247
144
DSTEKADLRLVYLALAHMIKFRGHFLIEGE-LNAENTDVQKL--FADFVGVYDRT--FDDS-H LSEITVDAS---SI
211


WP_002282906
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002283846
144
DNPEKTDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002287255
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002288990
144
DNPEKTDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002289641
144
DNPEKTDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002290427
144
DNPEKTDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002295753
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002296423
144
DNPEKTDLRLVYLALAHIIKFGGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002304487
144
NSTEKADLRLVYLSLAHMIKFRGHFLIEGQ-LKAENTNVQAL--FKDFVEVYDKT--VEES-H LSEMTVDAL---SI
211


WP_002305844
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002307203
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQKL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002310390
144
DNPEKTDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_002352408
144
DNPEKTDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_012997688
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_014677909
144
DNPEKTDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_019312892
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_019313659
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_019314093
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQKL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_019315370
144
DNPEKTDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_019803776
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_019805234
144
DNPEKTDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_024783594
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_024784288
144
DSTEKADLRLVYLALAHMIKFRGHFLIEGE-LNAENTDVQKL--FADFVGVYDRT--FDDS-H LSEITVDAS---SI
211


WP_024784666
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_024784894
144
DNPEKTDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_024786433
144
DSTEKADLRLVYLALAHMIKFRGHFLIEGE-LNAENTDVQKL--FADFVGVYDRT--FDDS-H LSEITVDAS---SI
211


WP_049473442
144
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


WP_049474547
144
DNPEKTDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
211


EMC03581
137
DNPEKVDLRLVYLALAHIIKFRGHFLIEGK-FDTRNNDVQRL--FQEFLAVYDNT--FENS-S LQEQNVQVE---EI
204


WP_000428612
145
DSKEKTDLRLIYLALAHMIKYRGHFLYEDT-FDIKNNDIQKI--FNEFISIYNNT--FEGN-S LSGQNVQVE---AI
212


WP_000428613
145
DSKEKTDLRLIYLALAHMIKYRGHFLYEDT-FDIKNNDIQKI--FSEFISIYDNT--FEGS-S LSGQNAQVE---AI
212


WP_049523028
144
DSKEKVDLRLIYLALAHIIKYRGHFLYEDS-FDIKNNDIQKI--FNEFTILYDNT--FEES-S LSKGNAQVE---EI
211


WP_003107102
113
DSDEKADLRLIYLALAHIIKFRGHFLIEGD-LDSQNTDVNAL--FLKLVDTYNLM--FEDD-- IDTQTIDAT---VI
180


WP_054279288
146
DNTEKADLRLIYLALAHIIKFRGHFLIEGA-LSANNTDVQQL--VHALVDAYNIM--FEED-- LDIEAIDVK---AI
213


WP_049531101
145
DSKEKADLRLIYLTLAHMIKYRGHFLYEES-FDIKNNDIQKI--FNEFISIYDNT--FEGS-S LSGQNAQVE---AI
212


WP_049538452
145
DSKEKADLRLIYLALAHMIKYRGHFLYEEA-FDIKNNDIQKI--FNEFINIYDNT--FEGS-S LSGQNEQVE---AI
212


WP_049549711
145
DSKEKADLRLIYLVLAHMIKYRGHFLYEEA-FDIKNNDIQKI--FNEFISIYDNT--FEGS-S LSGQNAQVE---TI
212


WP_007896501
146
DRDQKADLRLIYLALSHIIKFRGHFLIEGK-LNSENTDVQKL--FIALVTVYNLL--FEEE-- IAGETCDAK---AL
213


EFR44625
98
DRDQKADLRLIYLALSHIIKFRGHFLIEGK-LNSENTDVQKL--FIALVTVYNLL--FEEE-- IAGETCDAK---AL
165


WP_002897477
144
DSKEKSDVRLIYLALAHMIKYRGHFLYEET-FDIKNNDIQKI--FNEFINIYDNT--FEGS-S LSGQNAQVE---AI
211


WP_002906454
144
DSKEKTDLRLIYLALAHMIKYRGHFLYEES-FDIKNNDIQKI--FNEFISIYDNT--FEGS-S LSGQNAQVE---AI
211


WP_009729476
145
DSKEKTDLRLIYLALAHMIKYRGHFLYEEA-FDIKNNDIQKI--FNEFISIYNNT--FEGN-S LSGQNVQVE---AI
212


CQR24647
144
DSSEKADLRLVYLALAHIIKYRGHFLIDEP-IDIRNMNSQNL--FKEFLLAFDGI--QVDC-Y LASKHTDIS---GI
211


WP_000066813
145
DSKEKTDLRLIYLALAHMIKYRGHFLYEES-FDIKNNDIQKI--FSEFISIYDNT--FEGK-S LSGQNAQVE---AI
212


WP_009754323
145
DSKEKADLRLIYLALAHITKYRGHFLYEEA-FDIKNNDIQKI--FNEFINIYDNT--FEGS-S LSGQNAQVE---AI
212


WP_044674937
144
DSSQKADIRLIYLALAHIIKYRGHELFEGD-LKSENKDVQHL--FNDEVEMFDKT--VEGS-Y LSENLPNVA---DV
211


WP_044676715
144
DSSQKADIRLIYLALAHIIKYRGHELFEGD-LKSENKDVQHL--FNDEVEMFDKT--VEGS-Y LSENLPNVA---DV
211


WP_044680361
144
DSSQKADIRLIYLALAHIIKYRGHELFEGD-LKSENKDVQHL--FNDEVEMFDKT--VEGS-Y LSENLPNVA---DV
211


WP_044681799
144
DSSQKADIRLIYLALAHIIKYRGHELFEGD-LKSENKDVQHL--FNDEVEMFDKT--VEGS-Y LSENLPNVA---DV
211


WP_049533112
144
DISQKADLRLVYLALAHMIKERGHFLIEGQ-LKAENTNVQAL--FKDEVEVYDKT--VEES-H LSEMTVDAL---SI
211


WP_029090905
101
SQHRQFDIREVYLAIHHLIKYRGHFIYEDQtFTTDGNQLQHH--IKAIITMINST1---NR-- IIPETIDINvfeKI
171


WP_006506696
140
ESTEKADPRLIYLALHHIVKYRGNFLYEGQkFNMDASNIEDK--LSDIFTQFTSFnnIPYEdD --KKNLEIL---EI
210


AIT42264
144
DSTDKADLRLIYLALAHMIKERGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
211


WP_034440723
143
DSNQKADLRLIYLALAHMIKYRGHFLIEGD-LKMDGISISES--FQEFIDSYNEVcaLEDE-N NDELLTQIE---NI
217


AKQ21048
144
DSTDKADLRLIYLALAHMIKERGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
211


WP_004636532
144
DNPEKADLRLVYTALAHIVKYRGHFLIEGE-LNTENTSISET--FEQFLDTYSDI--FKEQ-- LVGDISKVE---EI
210


WP_002364836
144
DSSEQADLRLIYLALAHIVKYRGHFLIEGK-LSTENISVKEQ--FQQFMIIYNQT--FVNGeS PLPESVLIE---EE
217


WP_016631044
95
DSSEQADLRLIYLALAHIVKYRGHFLIEGK-LSTENTSVKDQ--FQQFMVIYNQT--FVNGeS PLPESVLIE---EE
168


EMS75795

--------------------------------------------------------------- --------------



WP_002373311
144
DSSEQADLRLIYLALAHIVKYRGHFLIEGK-LSTENTSVKEQ--FQQFMVIYNQT--FVNGeS PLPESVLIE---EE
217


WP_002378009
144
DSSEQADLRLIYLALAHIVKYRGHFLIEGK-LSTENISVKEQ--FQQFMIIYNQT--FVNGeS PLPESVLIE---EE
217


WP_002407324
144
DSSEQADLRLIYLALAHIVKYRGHFLIEGK-LSTENISVKEQ--FQQFMIIYNQT--FVNGeS PLPESVLIE---EE
217


WP_002413717
144
DSSEQADLRLIYLALAHIVKYRGHFLIEGK-LSTENISVKEQ--FQQFMIIYNQT--FVNGeS PLPESVLIE---EE
217


WP_010775580
144
DSSEQADLRLIYLALAHIVKYRGHFLIEGK-LSTENISVKEQ--FQQFMIIYNQT--FVNGeS PLPESVLIE---EE
217


WP_010818269
144
DSSEQADLRLIYLALAHIVKYRGHFLIEGK-LSTENISVKEQ--FQQFMIIYNQT--FVNGeS PLPESVLIE---EE
217


WP_010824395
144
DSSEQADLRLIYLALAHIVKYRGHFLIEGK-LSTENTSVKDQ--FQQFMVIYNQT--FVNGeS PLPESVLIE---EE
217


WP_016622645
144
DSSEQADLRLIYLALAHIVKYRGHFLIEGK-LSTENISVKEK--FQQFMIIYNQT--FVNGeG PLPESVLIE---EE
217


WP_033624816
144
DSSEQADLRLIYLALAHIVKYRGHFLIEGK-LSTENISVKDQ--FQQFMVIYNQT--FVNGeS PLPESVLIE---EE
217


WP_033625576
144
DSSEQADLRLIYLALAHIVKYRGHFLIEGK-LSTENISVKEQ--FQQFMIIYNQT--FVNGeS PLPESVLIE---EE
217


WP_033789179
144
DSSEQADLRLIYLALAHIVKYRGHFLIEGK-LSTENISVKEQ--FQQFMIIYNQT--FVNGeS PLPESVLIE---EE
217


WP_002310644
144
DSSEKADIRLVYLAMAHLLKYRGHFLIEGE-LNTENSSVTET--FRQFLSTYNQQ--FSEA-D KLDEAVDCS---FV
216


WP_002312694
144
DSSEKADIRLVYLAMAHLLKYRGHFLIEGE-LNTENSSVTET--FRQFLSTYNQQ--FSEA-G KLDEAVDCS---FV
216


WP_002314015
144
DSSEKADIRLVYLAMAHLLKYRGHFLIEGE-LNTENSSVTET--FRQFLSTYNQQ--FSEA-D KLDEAVDCS---FV
216


WP_002320716
144
DSSEKADIRLVYLAMAHLLKYRGHFLIEGE-LNTENSSVTET--FRQFLSTYNQQ--FSEA-D KLDEAVDCS---FV
216


WP_002330729
144
DSSEKADIRLVYLAMAHLLKYRGHFLIEGE-LNTENSSVTET--FRQFLSTYNQQ--FSEA-D KLDEAVDCS---FV
216


WP_002335161
144
DSSEKADIRLVYLAMAHLLKYRGHFLIEGE-LNTENSSVTET--FRQFLSTYNQQ--FSEA-D KLDEAVDCS---FV
216


WP_002345439
144
DSSEKADIRLVYLAMAHLLKYRGHFLIEGE-LNTENSSVTET--FRQFLSTYNQQ--FSEA-D KLDEAVDCS---FV
216


WP_034867970
144
DSTEKEDLRLVYLALAHLLKYRGHFLFEGD-LDTENTSIEES--FRVFLEQYSKQ--SDQP-- -LIVHQPVL---TI
209


WP_047937432
144
DSSEKADIRLVYLAMAHLLKYRGHFLIEGE-LNTENSSVTET--FRQFLSTYNQQ--FSEA-D KLDEAVDCS---FV
216


WP_010720994
144
DSTEKGDLRLVYLALAHLLKYRGHFLFEGD-LDTENTSIEES--FRVFLEQYGKQ--SDQP-- -LIVHQPVL---TI
209


WP_010737004
144
DSTEKEDLRLVYLALAHLLKYRGHFLFEGD-LDTENTSIEES--FRVFLEQYSKQ--SDQP-- -LIVHQPVL---TI
209


WP_034700478
144
DSTEKEDLRLVYLALAHLLKYRGHFLFEGD-LDTENTSIEES--FRVFLEQYGKQ--SDQP-- -LIVHQPVL---TI
209


WP_007209003
144
DGDEKADLRLVYLAIAHIIKFRGNFLIEGE-LNTENNSVIELs--KVFVQLYNQT1-SELE-- FIDESIDFS---EV
214


WP_023519017
144
NSKEQADIRLVYLAIAHCLKYRGHFLFEGE-LDTENTSVTEN--YQQFLQAYQQF--FPEP-- -IGDLDDAV---PI
209


WP_010770040
144
DTSEQADLRLVYLALAHIVKYRGHFLIEGE-LNTENSSVSET--FRTFIQVYNQI--FRENe- PLAVPDNIE---EL
212


WP_048604708
144
DAEEKADLRLVYLALAHIIKYRGHFLIEGR-LSTENTSTEET--FKTFLQKYNQT--FN---- PVDETISIG---SI
208


WP_010750235
144
DSTEKADIRLVYLALAHMIKYRGHFLFEGE-LDTENTSVEET--FKEFIDIYNEQ--FEEG-- -IIFYKDIP---LI
209


AII16583
183
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
250


WP_029073316
145
ESKEKEDPRLIYLALHHIVKYRGNFLYEGQkFSMDVSNIEDK--MIDVLRQFNEIn1FEYVeD --KKIDEVL---NV
215


WP_031589969
145
ESKEKEDPRLIYLALHHIVKYRGNFLYEGQkFSMDVSNIEDK--MIDVLRQFNEIn1FEYVeD --KKIDEVL---NV
215


KDA45870
145
NNDRPADLRLVYLALAHIIKYRGNELLEGE-IDLRTTDINKV--FAEFSETLNEN--SDEN1G ----KLDVA---DI
209


WP_039099354
133
TEKRQFDIREIYLAMHHIVKYRGHFLNEAPvSSEKSSEINLVahFDRLNTIFADL--FSESgF -TDKLAEVK---AL
206


AKP02966
138
INKNKADIRLVYLALHNILKYRGNFTYEHQkFNISTLNSNLS---KELIELNQQLikYDIS-- -FPDNCDWNhisDI
208


WP_010991369
144
NSSEKADLRLVYLALAHIIKYRGNFLIEGA-LDTQNTSVDGI--YKQFIQTYNQV--FASGiE KLEDNKDVA---KI
217


WP_033838504
144
NSSEKADLRLVYLALAHIIKYRGNFLIEGA-LDTQNTSVDGI--YKQFIQTYNQV--FASGiE KLEDNKDVA---KI
217


EHN60060
147
NSSEKADLRLVYLALAHIIKYRGNFLIEGA-LDTQNTSVDGI--YKQFIQTYNQV--FASGiE KLEDNKDVA---KI
220


EFR89594

--------------------------------------------------------------- --------------



WP_038409211
144
NSSDKADLRLVYLALAHIIKYRGNFLIEGM-LDTKNTSVDEV--FKQFIQTYNQI--FASDiE RLEENKEVA---EI
217


EFR95520

--------------------------------------------------------------- --------------



WP_003723650
144
NSSEKADLRLVYLALAHIIKYRGNFLIEGA-LDTKNTSVDEV--YKQFIETYNQV--FMSNiE KVEENIEVA---NI
217


WP_003727705
144
NSSEKADLRLVYLALAHIIKYRGNFLIEGA-LDTKNTSVDEV--YKQFIQTYNQV--FMSNiE KVEENTEVA---SI
217


WP_003730785
144
NSSEKADLRLVYLALAHIIKYRGNFLIEGA-LDTKNTSVDEV--YKQFIQTYNQV--FMSNiE KVEENTEVA---SI
217


WP_003733029
144
DSQKKADLRLVYLALAHIIKYRGHFLIEGA-LDTKNTSIDEM--FKQFLQIYNQV--FANDiE KTEKNQEVA---QI
217


WP_003739838
144
NSSEKADLRLVYLALAHIIKYRGNFLIEGA-LDTKNTSVDGV--YKQFIQTYNQV--FISNiE KMEENTTVA---DI
217


WP_014601172
144
NSSEKADLRLVYLALAHIIKYRGNFLIEGA-LDTKNTSVDGV--YEQFIQTYNQV--FMSNiE KVEENIEVA---NI
217


WP_023548323
144
NSSEKADLRLVYLALAHIIKYRGNFLIEGA-LDTKNTSVDGV--YEQFILTYNQV--FMSNiE KVEENIEVA---NI
217


WP_031665337
144
NSSEKADLRLVYLALAHIIKYRGNFLIEGA-LDTKNTSVDGV--YEQFIQTYNQV--FMSNiE KVEENIEVA---NI
217


WP_031669209
144
DSQKKADLRLVYLALAHIIKYRGHFLIEGA-LDTKNTSIDEM--FKQFLQIYNQV--FANDiE KTEKNQEVA---QI
217


WP_033920898
144
NSSEKADLRLVYLALAHIIKYRGNFLIEGA-LDTKNTSVDGV--YEQFIQTYNQV--FMSNiE KVEENIEVA---NI
217


AKI42028
147
NSSEKADLRLVYLALAHIIKYRGNFLIEGA-LDTKNTSVDGV--YEQFIQTYNQV--FMSNiE KVEENIEVA---NI
220


AKI50529
147
NSSEKADLRLVYLALAHIIKYRGNFLIEGA-LDTKNTSVDGV--YEQFIQTYNQV--FMSNiE KVEENIEVA---NI
220


EFR83390

--------------------------------------------------------------- --------------



WP_046323366
144
NSSDKADLRLVYLALAHIIKYRGNFLIEGK-LDTKNTSVDEV--FKQFIKTYNQV--FASDiE RIEENNEVA---KI
217


AKE81011
160
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
227


CUO82355
144
ESTEKADPRLIYLALHHIVKYRGNFLYEGQkFNMDASNIEDK--LSDVFTQFADFnnIPYEdD --KKNLEIL---EI
214


WP_033162887
145
ENKEKADPRLIYLALHHIVKYRGNFLYEGQsFTMDNSDIEER--LNSAIEKFMSIneFDNRiV --SDINSMI---AV
215


AGZ01981
177
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
244


AKA60242
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
211


AKS40380
144
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
211


4UN5_B
148
DSTDKADLRLIYLALAHMIKFRGHFLIEGD-LNPDNSDVDKL--FIQLVQTYNQL--FEEN-- INASGVDAK---AI
215


WP_010922251
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-custom character ---KLQ--LSKDTYDDDLDN
277


WP_039695303
213
LTEK-ISKSRRLENLIKY-Y-PT EKKNTLFGNLIALALGLQPNFKTNF--KLSED-A---KLQ--FSKDTYEEDLEE
278


WP_045635197
212
FTDK-ISKSAKRERVLKL-F-PD EKSTGLFSEFLKLIVGNQADFKKHF--DLEDK-A---PLQ--FSKDTYDEDLEN
277


5AXW_A
135
LSTK--------EQISRN-S--K ------------------LEEKyVa--ELQ------------------------
157


WP_009880683

------- ----------------------



WP_010922251
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_011054416
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_011284745
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_011285506
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_011527619
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_012560673
212
LSAR-LSKSRRLENLIAQ-L-PG EKRNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_014407541
212
LSAR-LSKSRRLENLIAQ-L-PG EKRNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_020905136
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_023080005
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_023610282
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_030125963
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_030126706
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_031488318
212
LSAR-LSKSRRLENLIAQ-L-PG EKRNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_032460140
212
LSAR-LSKSRRLENLIAQ-L-PG EKRNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_032461047
212
LSAR-LSKSRRLENLIAQ-L-PG EKRNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_032462016
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_032462936
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALLLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_032464890
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_033888930
37
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
102


WP_038431314
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_038432938
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-T---KLQ--LSKDTYDDDLDN
277


WP_038434062
212
LSAR-LSKSRRLENLIAQ-L-PG EKRNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


BAQ51233
123
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
188


KGE60162

----------------------- ------------------------------------------------------



KGE60856

----------------------- ------------------------------------------------------



WP_002989955
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_003030002
212
LTEK-VSKSRRLENLIAH-Y-PA EKKNTLFGNLIALSLGLQPNFKTNF--QLSED-A---KLQ--FSKDTYEEDLEG
277


WP_003065552
215
LTEK-ISKSRRLENLIKY-Y-PT EKKNTLFGNLIALALGLQPNFKMNF--KLSED-A---KLQ--FSKDSYEEDLGE
280


WP_001040076
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040078
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040080
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040081
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040083
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040085
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040087
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040088
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040089
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040090
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040091
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040092
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040094
213
LTDK-ISKSAKKDRILAR-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040095
213
LTDK-ISKSAKKDRILAR-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040096
213
LTDK-ISKSAKKDRILAR-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040097
213
LTDK-ISKSAKKDRILAR-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040098
213
LTDK-ISKSAKKDRILAR-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040099
213
LTDK-ISKSAKKDRILAR-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040100
213
LTDK-ISKSAKKDRILAR-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040104
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040105
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040106
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040107
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040108
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040109
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_001040110
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_015058523
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_017643650
213
LTDK-ISKSAKKDRILAR-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_017647151
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_017648376
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_017649527
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_017771611
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_017771984
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


CFQ25032
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


CFV16040
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


KLJ37842
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


KLJ72361
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


KLL20707
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


KLL42645
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_047207273
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_047209694
213
LTDK-ISKSAKKDRILAR-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_050198062
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_050201642
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_050204027
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_050881965
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_050886065
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


AHN30376
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


EA078426
213
LTDK-ISKSAKKDRILAQ-Y-PN QKSTGIFAEFLKLIVGNQADFKKYF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


CCW42055
213
LTDK-ISKSAKKDRILAQ-Y-PD QKSTGIFAEFLKLIVGNQADFKKHF--NLEDK-T---PLQ--FAKDSYDEDLEN
278


WP_003041502
212
LTEK-VSKSRRLENLIAH-Y-PA EKKNTLFGNLIALFLGLQPNFKTNF--QLSED-A---KLQ--FSKDTYEEDLEG
277


WP_037593752
213
LTEK-VSKSSRLENLIAH-Y-PT EKKNTLFGNLIALSLGLQPNFKTNF--QLSED-A---KLQ--FSKDTYEEDLEE
278


WP_049516684
213
LTEK-VSKSRRLENLVEC-Y-PT EKKNTLFGNLIALSLGLQPNFKTNF--QLSED-A---KLQ--FSKDTYEEDLEG
278


GAD46167
212
LTEK-VSKSSRLENLIAH-Y-PT EKKNTLFGNLIALSLGLQPNFKTNF--QLSED-A---KLQ--FSKDTYEEDLEE
277


WP_018363470
213
LTEK-ISKSRRLENLINN-Y-PK EKKNTLFGNLIALALGLQPNFKTNF--KLSED-A---KLQ--FSKDTYEEDLEE
278


WP_003043819
212
LSAR-LSKSKRLEKLIAV-F-PN EKKNGLFGNIIALALGLTPNFKSNF--DLTED-A---KLQ--LSKDTYDDDLDE
277


WP_006269658
212
LTEK-VSKSSRLENLIAH-Y-PT EKKNTLFGNLIALSLDLHPNFKTNF--QLSED-A---KLQ--FSKDTYEEDLEG
277


WP_048800889
212
LTEK-VSKSRRLENLVKC-Y-PT EKKNTLFGNLIALSLGLQPNFKTNF--QLSED-A---KLQ--FSKDTYEEDLEE
277


WP_012767106
212
LSAR-LSKSRRLENLIAQ-L-PG EKRNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_014612333
212
LSAR-LSKSKRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_015017095
212
LSAR-LSKSRRLENLIAQ-L-PG EKRNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_015057649
212
LSAR-LSKSRRLENLIAQ-L-PG EKRNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_048327215
212
LSAR-LSKSRRLENLIAQ-L-PG EKRNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_049519324
212
LSAR-LSKSRRLENLIAQ-L-PG EKRNGLFGNLIALSLGLTPNFKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_012515931
212
LSAA-LSKSKRLENLISL-I-PG QKKTGIFGNIIALSLGLTPNFKANF--GLSKD-V---KLQ--LAKDTYADDLDS
277


WP_021320964
212
LSAA-LSKSKRLENLISL-I-PG QKKTGIFGNIIALSLGLTPNFKANF--GLSKD-V---KLQ--LAKDTYADDLDS
277


WP_037581760
212
LSAA-LSKSKRLENLISL-I-PG QKKTGIFGNIIALSLGLTPNFKANF--GLSKD-V---KLQ--LAKDTYADDLDS
277


WP_004232481
212
LTEK-ISKSRRLENLIKQ-Y-PT EKKNTLFGNLVALALGLQPNFKTNF--KLSED-A---KLQ--FSKDTYDEDLEE
277


WP_009854540
213
LTEK-ISKSRRLENLIKY-Y-PT EKKNTLFGNLIALALGLQPNFKMNF--KLSED-A---KLQ--FSKDTYEEDLEE
278


WP_012962174
213
LTEK-FSKSRRLENLIKH-Y-PT EKKNTLFGNLVALALGLQPNFKTSF--KLSED-A---KLQ--FSKDTYEEDLEE
278


WP_039695303
213
LTEK-ISKSRRLENLIKY-Y-PT EKKNTLFGNLIALALGLQPNFKTNF--KLSED-A---KLQ--FSKDTYEEDLEE
278


WP_014334983
212
LTEK-VSKSRRLENLIKQ-Y-PT EKKNTLFGNLIALALGLQPNFKTNF--KLSED-A---KLQ--FSKDTYEEDLEE
277


WP_003099269
212
LTSK-TSKSRRLENLIAE-I-PN QKRNMLFGNLVSLALGLTPNFKTNF--ELLED-A---KLQ--ISKDSYEEDLDN
277


AHY15608
212
LTSK-TSKSRRLENLIAE-I-PN QKRNMLFGNLVSLALGLTPNFKTNF--ELLED-A---KLQ--ISKDSYEEDLDN
277


AHY17476
212
LTSK-TSKSRRLENLIAE-I-PN QKRNMLFGNLVSLALGLTPNFKTNF--ELLED-A---KLQ--ISKDSYEEDLDN
277


ESR09100

----------------------- ------------------------------------------------------



AGM98575
212
LTSK-TSKSRRLENLIAE-I-PN QKRNMLFGNLVSLALGLTPNFKTNF--ELLED-A---KLQ--ISKDSYEEDLDN
277


ALF27331
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_018372492
210
FTEN-SSKAKRVETILGL-F-PD ETAAGNLDKFLKLMLGNQADFKKVF--DLEEK----iTLQ--FSKDSYEEDLEL
275


WP_045618028
213
FTDK-ISKSAKRERVLKL-F-PD EKSTGLFSEFLKLIVGNQADFKKHF--DLEEK-A---PLQ--FSKDTYDEDLEN
278


WP_045635197
212
FTDK-ISKSAKRERVLKL-F-PD EKSTGLFSEFLKLIVGNQADFKKHF--DLEDK-A---PLQ--FSKDTYDEDLEN
277


WP_002263549
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_002263887
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_002264920
212
LTEK-ISKSRRLEKLINN-Y-PK EKKNTLFRNLVALSLGLQPNFKTNF--KLSED-A---KLQ--FSKDTYEEDLEE
277


WP_002269043
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDIYEEELEV
277


WP_002269448
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_002271977
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEDLEE
277


WP_002272766
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEDLEE
277


WP_002273241
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_002275430
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_002276448
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_002277050
212
LTEK-ISKSRRLEKLINN-Y-PK EKKNTLFGNLIALSLGLQPNFKTNF--KLSED-A---KLQ--FSKDTYEEDLEE
277


WP_002277364
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_002279025
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_002279859
212
LTEK-ISKSRRLEKLINN-Y-PK EKKNTLFGNLIALSLGLQPNFKTNF--KLSED-A---KLQ--FSKDTYEEELEV
277


WP_002280230
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_002281696
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_002282247
212
LTEK-ISKSRRLEKLINN-Y-PK EKKNTLFGNLIALSLGLQPNFKTNF--KLSED-A---KLQ--FSKDTYEEDLEE
277


WP_002282906
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_002283846
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDIYEEELEV
277


WP_002287255
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_002288990
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDIYEEELEV
277


WP_002289641
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGCFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_002290427
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDIYEEELEV
277


WP_002295753
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_002296423
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDIYEEELEV
277


WP_002304487
212
LTEK-VSKSRRLENLVEC-Y-PT EKKNTLFGNLIALSLGLQPNFKTNF--QLSED-A---KLQ--FSKDTYEEDLEG
277


WP_002305844
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_002307203
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--LSKDTYEEELEV
277


WP_002310390
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDIYEEELEV
277


WP_002352408
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDIYEEELEV
277


WP_012997688
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_014677909
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDIYEEELEV
277


WP_019312892
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_019313659
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIIGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_019314093
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--LSKDTYEEELEV
277


WP_019315370
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_019803776
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-V---PLQ--FSKDTYEEELEV
277


WP_019805234
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDIYEEELEV
277


WP_024783594
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_024784288
212
LTEK-ISKSRRLEKLINN-Y-PK EKKNTLFGNLIALSLGLQPNFKTNF--KLSED-A---KLQ--FSKDTYEEDLEE
277


WP_024784666
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_024784894
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


WP_024786433
212
LTEK-ISKSRRLEKLINN-Y-PK EKKNTLFGNLIALSLGLQPNFKTNF--KLSED-A---KLQ--FSKDTYEEDLEE
277


WP_049473442
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEDLEE
277


WP_049474547
212
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
277


EMC03581
205
LTDK-ISKSAKKDRVLKL-F-PN EKSNGRFAEFLKLIVGNQADFKKHF--ELEEK-A---PLQ--FSKDTYEEELEV
270


WP_000428612
213
FTDK-ISKSAKRERVLKL-F-PD EKSTGLFSEFLKLIVGNQADFKKHF--DLEEK-A---PLQ--FSRDTYDEDLEN
278


WP_000428613
213
FTDK-ISKSAKRERVLKL-F-PD EKSTGLFSEFLKLIVGNQADFKKHF--DLGEK-A---PLQ--FSKDTYDEDLEN
278


WP_049523028
212
FTDK-ISKSAKRDRVLKL-F-PD EKSTGLFSEFLKLIVGNQADFKKHF--DLEEK-A---PLQ--FSKDTYEEDLES
277


WP_003107102
181
LTEK-MSKSRRLENLIAK-I-PN QKKNTLFGNLISLSLGLTPNFKANF--ELSED-A---KLQ--ISKESFEEDLDN
246


WP_054279288
214
LTEK-ISKTRRLENLISN-I-PG QKKNGLFGNLIALSLGLTPNFKSHF--NLPED-A---KLQ--LAKDTYDEELNN
279


WP_049531101
213
FTDK-ISKSTKRERVLKL-F-PD QKSTGLFSEFLKLIVGNQADFKKHF--DLEEK-A---PLQ--FSKDTYDEDLEN
278


WP_049538452
213
FSDK-ISKSAKRERVLKL-F-PD EKSTGLFSEFLKLIVGNQADFKKHF--DLEEK-A---PLQ--FSKDTYDEDLEN
278


WP_049549711
213
FTDK-ISKSAKRERVLKL-F-PD EKSTGLFSEFLKLIVGNQADFKKHF--DLGEK-A---PLQ--FSKDTYDEDLEN
278


WP_007896501
214
LTAK-TSKSKRLESLISE-F-PG QKKNGLFGNLLALALGLRPNFKSNF--GLSED-A---KLQ--ITKDTYEEELDN
279


EFR44625
166
LTAK-TSKSKRLESLISE-F-PG QKKNGLFGNLLALALGLRPNFKSNF--GLSED-A---KLQ--ITKDTYEEELDN
231


WP_002897477
212
FTDK-ISKSAKRERVLKL-F-PD EKSTGLFSEFLKLIVGNQADFKKHF--DLEEK-A---PLQ--FSKDTYDEELEN
277


WP_002906454
212
FTDK-ISKSTKRERVLKL-F-SD EKSTGLFSEFLKLIVGNQADFKKHF--DLEEK-A---PLQ--FSKDTYDEDLEN
277


WP_009729476
213
FTDK-ISKSAKRERVLKL-F-PD EKSTGLFSEFLKLIVGNQADFKKHF--DLEEK-A---PLQ--FSRDTYDEDLEN
278


CQR24647
212
ITAK-ISKSRKVEAVLEQ-F-PD QKKNSFFGNMVSLVFGLMPNEKSNF--ELDED-A---KLQ--FSRDSYDEDLEN
277


WP_000066813
213
FTDK-ISKSTKRERVLKL-F-PD EKSTGLFSEFLKLIVGNQADFKKHF--DLEEK-A---PLQ--FSKDTYDEDLEN
278


WP_009754323
213
FTGK-ISKSVKREHVLKL-F-PD EKSTGLFSEFLKLIVGNQADFKKHF--DLEEK-A---SLQ--FSKDTYDEDLEN
278


WP_044674937
212
LVEK-VSKSRRLENILHY-F-PN EKKNGLFGNFLALALGLQPNEKTNF--ELAED-A---KIQ--FSKETYEEDLEE
277


WP_044676715
212
LVEK-VSKSRRLENILHY-F-PN EKKNGLFGNFLTLALGLQPNEKTNF--ELAED-A---KIQ--FSKETYEEDLEE
277


WP_044680361
212
LVEK-VSKSRRLENILHY-F-PN EKKNGLFGNFLALALGLQPNEKTNF--ELAED-A---KIQ--FSKETYEEDLEE
277


WP_044681799
212
LVEK-VSKSRRLENILHY-F-PN EKKNGLFGNFLALALGLQPNEKTNF--ELAED-A---KIQ--FSKETYEEDLEE
277


WP_049533112
212
LTEK-VSKSRRLENLIAH-Y-PA EKKNTLFGNLIALSLGLQPNEKTNF--QLSED-A---KLQ--FSKDTYEEDLEG
277


WP_029090905
172
LLDRmMNRSSKVKFLIEL---TG KQDKPLLKELFNLIVGLKAKPASIFe---QEN1AtivETM-nMSTEQVQLDLLT
243


WP_006506696
211
LKKP-LSKKAKVDEVMTL-IaPE KDYKSAFKELVTGIAGNKMNVTKMI1cEPIKQ-Gds-EIK1kFSDSNYDDQFSE
283


AIT42264
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNEKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_034440723
218
FKQD-ISRSKKLDQAIAL-F-QG -KRQSLFGIFLTLIVGNKANFQKIF--NLEDD----iKLD--LKEEDYDENLEE
283


AKQ21048
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNEKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


WP_004636532
211
LSSK-QSRSRKHEQIMAL-F-PN ENKLGNFGRFMMLIVGNTSNFKPVF--DLDDE-Y---KLK--LSDETYEEDLDT
276


WP_002364836
218
LTEK-ASRTKKSEKVLQQ-F-PQ EKANGLFGQFLKLMVGNKADFKKVF--GLEEE-A---KI--tYASESYEEDLEG
283


WP_016631044
169
LTEK-ASRTKKSEKVLQQ-F-PQ EKANGLFGQFLKLMVGNKADFKKVF--GLEEE-A---KI--tYASESYEEDLEG
234


EM575795
1
----------------------- ----------------------------MDEE-A---KIQ--LSKESYEEELES
20


WP_002373311
218
LTEK-ASRTKKSEKVLQQ-F-PQ EKANGLFGQFLKLMVGNKADFKKVF--GLEEE-A---KI--tYASESYEEDLEG
283


WP_002378009
218
LTEK-ASRTKKSEKVLQQ-F-PQ EKANGLFGQFLKLMVGNKADFKKVF--GLEEE-A---KI--tYASESYEEDLEG
283


WP_002407324
218
LTEK-ASRTKKSEKVLQQ-F-PQ EKANGLFGQFLKLMVGNKADFKKVF--GLEEE-A---KI--tYASESYEEDLEG
283


WP_002413717
218
LTEK-ASRTKKSEKVLQQ-F-PQ EKANGLFGQFLKLMVGNKADFKKVF--GLEEE-A---KI--tYASESYEEDLEG
283


WP_010775580
218
LTEK-ASRTKKSEKVLQQ-F-PQ EKANGLFGQFLKLMVGNKADFKKVF--GLEEE-A---KIKitYASESYEEDLEG
285


WP_010818269
218
LTEK-ASRTKKSEKVLQQ-F-PQ EKANGLFGQFLKLMVGNKADFKKVF--GLEEE-A---KI--tYASESYEEDLEG
283


WP_010824395
218
LTEK-ASRTKKSEKVLQQ-F-PQ EKANGLFGQFLKLMVGNKADFKKVF--GLEEE-A---KI--tYASESYEEDLEG
283


WP_016622645
218
LTEK-ASRTKKSEKVLQQ-F-PQ EKANGLFGQFLKLMVGNKADFKKVF--GLEEE-A---KI--tYASESYEEDLEG
283


WP_033624816
218
LTEK-ASRTKKSEKVLQQ-F-PQ EKANGLFGQFLKLMVGNKADFKKVF--GLEEE-A---KI--tYASESYEEDLEG
283


WP_033625576
218
LTEK-ASRTKKSEKVLQQ-F-PQ EKANGLFGQFLKLMVGNKADFKKVF--GLEEE-A---KI--tYASESYEEDLEG
283


WP_033789179
218
LTEK-ASRTKKSEKVLQQ-F-PQ EKANGLFGQFLKLMVGNKADFKKVF--GLEEE-A---KI--tYASESYEEDLEG
283


WP_002310644
217
FTEK-MSKTKKAETLLKY-F-PH EKSNGYLSQFIKLMVGNQGNFKNVF--GL-EE-A---KLQ--FSKETYEEDLEE
281


WP_002312694
217
FTEK-MSKTKKAETLLKY-F-PH EKSNGYLSQFIKLMVGNQGNFKNVF--GL-EEeA---KLQ--FSKETYEEDLEE
282


WP_002314015
217
FTEK-MSKTKKAETLLKY-F-PH EKSNGYLSQFIKLMVGNQGNFKNVF--GL-EEeA---KLQ--FSKETYEEDLEE
282


WP_002320716
217
FTEK-MSKTKKAETLLKY-F-PH EKSNGYLSQFIKLMVGNQGNFKNVF--GL-EEeA---KLQ--FSKETYEEDLEE
282


WP_002330729
217
FTEK-MSKTKKAETLLKY-F-PH EKSNGYLSQFIKLMVGNQGNFKNVF--GL-EE-A---KLQ--FSKETYEEDLEE
281


WP_002335161
217
FTEK-MSKTKKAETLLKY-F-PH EKSNGYLSQFIKLMVGNQGNFKNVF--GL-EEeA---KLQ--FSKETYEEDLEE
282


WP_002345439
217
FTEK-MSKTKKAETLLKY-F-PH EKSNGYLSQFIKLMVGNQGNFKNVF--GL-EEeA---KLQ--FSKETYEEDLEE
282


WP_034867970
210
LTDK-LSKTKKVEEILKY-Y-PT EKINSFFAQCLKLIVGNQANFKRIF--DLEAE-V---KLQ--FSKETYEEDLES
275


WP_047937432
217
FTEK-MSKTKKAETLLKY-F-PH EKSNGYLSQFIKLMVGNQGNFKNVF--GL-EEeA---KLQ--FSKETYEEDLEE
282


WP_010720994
210
LTDK-LSKTKKVEEILKY-Y-PT EKINSFFAQCLKLIVGNQANFKRIF--DLEAE-V---KLQ--FSKETYEEDLES
275


WP_010737004
210
LTDK-LSKTKKVEEILKY-Y-PT EKINSFFAQCLKLIVGNQANFKRIF--DLEAE-V---KLQ--FSKETYEEDLES
275


WP_034700478
210
LTDK-LSKTKKVEEILKY-Y-PT EKINSFFAQCLKLIVGNQANFKRIF--DLEAE-V---KLQ--FSKETYEEDLES
275


WP_007209003
215
LTQQ-LSKSERADNVLKL-F-PD EKGTGIFAQFIKLIVGNQGNFKKVF--QLEED----qKLQ--LSTDDYEENIEN
280


WP_023519017
210
LTER-LSKAKRVEKVLAY-Y-PS EKSTGNFAQFLKLMVGNQANFKKTF--DLEEE-M---KLN--FTRDCYEEDLNE
275


WP_010770040
213
FSEK-VSRARKVEAILSV-Y-SE EKSTGTLAQFLKLMVGNQGRFKKTF--DLEED-G---IIQ--IPKEEYEEELET
278


WP_048604708
209
FADK-VSRAKKAEGVLAL-F-PD EKRNGTFDQFLKMIVGNQGNFKKTF--ELEED-A---KLQ--FSKEEYDESLEA
274


WP_010750235
210
LTDK-LSKSKKVEKILQY-Y-PK EKTTGCLAQFLKLIVGNQGNFKQAF--HLDEE-V---KIQ--ISKETYEEDLEK
275


AII16583
251
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLFGNLIALSLGLTPNEKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
316


WP_029073316
216
LKEP-LSKKHKADKAFAL-FdTT KDNKAAYKELCAALAGNKFNVTKMLkeAELHD-EdekDISfkFSDATFDDAFVE
289


WP_031589969
216
LKEP-LSKKHKAEKAFAL-FdTT KDNKAAYKELCAALAGNKFNVTKMLkeAELHD-EdekDISfkFSDATFDDAFVE
289


KDA45870
210
FKDNtFSKTKKSEELLKL---SG -KKNQLAHQLFKMMVGNMGSFKKVL--GTDEE----hKLS--FGKDTYEDDLND
275


WP_039099354
207
LLDNhQSASNRQRQALLLiYtPS KQNKAIATELLKAILGLKAKFNVLT--GIEAEdVktwTLT--FNAENFDEEMVK
285


AKP02966
209
LIGR-GNATQKSSNILNN-F--T KETKKLLKEVINLILGNVAHLNTIFktSLTKDeE---KLS--FSGKDIESKLDD
278


WP_010991369
218
LVEK-VTRKEKLERILKL-Y-PG EKSAGMFAQFISLIVGSKGNFQKPF--DLIEK-S---DIE--CAKDSYEEDLES
283


WP_033838504
218
LVEK-VTRKEKLERILKL-Y-PG EKSAGMFAQFISLIVGSKGNFQKPF--DLIEK-S---DIE--CAKDSYEEDLES
283


EHN60060
221
LVEK-VTRKEKLERILKL-Y-PG EKSAGMFAQFISLIVGSKGNFQKPF--DLIEK-S---DIE--CAKDSYEEDLES
286


EFR89594
1
---------------LKL-Y-PG EKSTGMFAQFISLIVGSKGNFQKPF--DLIEK-S---DIE--CAKDSYEEDLES
52


WP_038409211
218
LSEK-LTRREKLDKILKL-Y-TG EKSTGMFARFINLIIGSKGDFKKVF--DLDEK-A---EIE--CAKDTYEEDLEA
283


EFR95520

----------------------- ------------------------------------------------------



WP_003723650
218
LAGK-FTRREKFERILQL-Y-PG EKSTGMFAQFISLIVGSKGNFQKVF--DLIEK-T---DIE--CAKDSYEEDLET
283


WP_003727705
218
LAGK-FTRREKFERILRL-Y-PG EKSTGMFAQFISLIVGNKGNFQKVF--NLVEK-T---DIE--CAKDSYEEDLEA
283


WP_003730785
218
LAGK-FTRREKFERILRL-Y-PG EKSTGMFAQFISLIVGNKGNFQKVF--NLVEK-T---DIE--CAKDSYEEDLEA
283


WP_003733029
218
LAEK-FTRKDKLDKILSL-Y-PG EKTTGVFAQFVNIIVGSTGKEKKHF--NLHEK-K---DIN--CAEDTYDTDLES
283


WP_003739838
218
LAGK-FTRKEKLERILQL-Y-PG EKSTGMFAQFISLIVGSKGNFQKVF--DLVEK-T---DIE--CAKDSYEEDLEA
283


WP_014601172
218
LAGK-FTRREKFERILQL-Y-PG EKSTGMFAQFISLIVGSKGNFQKVF--DLIEK-T---DIE--CAKDSYEEDLEA
283


WP_023548323
218
LAGK-FTRREKFERILQL-Y-PG EKSTGMFAQFISLIVGSKGNFQKVF--DLIEK-T---DIE--CAKDSYEEDLET
283


WP_031665337
218
LAGK-FTRREKFERILQL-Y-PG EKSTGMFAQFISLIVGSKGNFQKVF--DLIEK-T---DIE--CAKDSYEEDLET
283


WP_031669209
218
LAEK-FTRKDKLDKILSL-Y-PG EKTTGVFAQFVNIIVGSTGKEKKHF--NLHEK-K---DIN--CAEDTYDTDLES
283


WP_033920898
218
LARK-FTRREKFERILQL-Y-PG EKSTGMFAQFISLIVGSKGNFQKVF--DLIEK-T---DIE--CAKDSYEEDLET
283


AKI42028
221
LAGK-FTRREKFERILQL-Y-PG EKSTGMFAQFISLIVGSKGNFQKVF--DLIEK-T---DIE--CAKDSYEEDLEA
286


AKI50529
221
LARK-FTRREKFERILQL-Y-PG EKSTGMFAQFISLIVGSKGNFQKVF--DLIEK-T---DIE--CAKDSYEEDLET
286


EFR83390

----------------------- ------------------------------------------------------



WP_046323366
218
FSEK-LTKREKLDKILNL-Y-PN EKSTDLFAQFISLIIGSKGNEKKFF--NLTEK-T---DIE--CAKDSYEEDLEV
283


AKE81011
228
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLEGNLIALSLGLTPNEKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
293


CUO82355
215
LKKP-LSKKAKVDEVMAL-IsPE KEFKSAYKELVTGIAGNKMNVTKMIlcESIKQ-Gds-EIK1kFSDSNYDDQFSE
287


WP_033162887
216
LSKI-YQRSKKADDLLKI-MnPT KEEKAAYKEFTKALVGLKFNISKMIlaQEVKK-Gdt-DIV1eFSNANYDSTIDE
288


AGZ01981
245
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLEGNLIALSLGLTPNEKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
310


AKA60242
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLEGNLIALSLGLTPNEKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


AKS40380
212
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLEGNLIALSLGLTPNEKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
277


4UN5_B
216
LSAR-LSKSRRLENLIAQ-L-PG EKKNGLEGNLIALSLGLTPNEKSNF--DLAED-A---KLQ--LSKDTYDDDLDN
281


WP_010922251
278
LLAQIGDQYADLFLAAcustom character NLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_039695303
279
LLGKIGDDYADLFTSAKNLYDAILLSGILTVDDNSTKAPLSASMIKRYVEHHEDLEKLKEFIKAN-KSELYHDIFKDKNK
357


WP_045635197
278
LLGQIGDDFTDLFVSAKKLYDAILLSGILTVTDPSTKAPLSASMIERYENHQNDLAALKQFIKNN-LPEKYDEVFSDQSK
356


5AXW_A
158
---------------------------------------------------------LERLKKDG-------EVR-----
168


WP_009880683
1
---------------------------------------LSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
40


WP_010922251
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_011054416
278
LLAQIGDQYADLFLAAKNLSDATLLSDILRVNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_011284745
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRLNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_011285506
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_011527619
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRLNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_012560673
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_014407541
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_020905136
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRLNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_023080005
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_023610282
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_030125963
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKASLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_030126706
278
LLAQIGDQYADLFLAAKNLSDATLLSDILRVNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_031488318
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_032460140
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_032461047
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_032462016
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_032462936
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_032464890
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRLNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_033888930
103
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
181


WP_038431314
278
LLAQIGDQYADLFLAAKNLSDATLLSDILRVNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_038432938
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_038434062
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


BAQ51233
189
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
267


KGE60162

--------------------------------------------------------------------------------



KGE60856

--------------------------------------------------------------------------------



WP_002989955
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRLNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_003030002
278
LLGEIGDEYADLFASAKNLYDAILLSGILTVDDNSTKAPLSASMVKRYEEHQKDLKKLKDFIKVN-APDQYNAIFKDKNK
356


WP_003065552
281
LLGKIGDDYADLFTSAKNLYDAILLSGILIVDDNSTKAPLSASMIKRYVEHQEDLEKLKEFIKAN-KSELYHDIFKDKNK
359


WP_001040076
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIVADSSK
357


WP_001040078
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040080
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040081
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040083
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040085
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040087
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040088
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040089
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040090
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040091
279
LLRQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040092
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVTDLSTKAPLSAYMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040094
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVTDLSTKAPLSASMIQHYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040095
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040096
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040097
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040098
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040099
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040100
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040104
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040105
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_001040106
279
LLGQIGDEFADLFSVAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFTDSSK
357


WP_001040107
279
LLGQIGDEFADLFSVAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFTDSSK
357


WP_001040108
279
LLGQIGDEFADLFSVAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFTDSSK
357


WP_001040109
279
LLGQIGDEFADLFSVAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFTDSSK
357


WP_001040110
279
LLGQIGDEFADLFSVAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFTDSSK
357


WP_015058523
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_017643650
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_017647151
279
LLGQIGDEFADLFSVAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFTDSSK
357


WP_017648376
279
LLGQIGDEFADLFSVAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFTDSSK
357


WP_017649527
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_017771611
279
LLGQIGDEFADLFSVAKKLYDSVLLSGILTVTALSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFTDSSK
357


WP_017771984
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


CFQ25032
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKASLSDSMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


CFV16040
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


KLJ37842
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


KLJ72361
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


KLL20707
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


KLL42645
279
LLGQIGDEFADLFSVAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFTDSSK
357


WP_047207273
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_47209694
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_050198062
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_050201642
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_050204027
279
LLGQIGDEFADLFSVAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFTDSSK
357


WP_050881965
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_050886065
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


AHN30376
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


EA078426
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVIDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


CCW42055
279
LLGQIGDEFADLFSAAKKLYDSVLLSGILTVTDLSTKAPLSASMIQRYDEHREDLKQLKQFVKAS-LPEKYQEIFADSSK
357


WP_003041502
278
LLGEVGDEYADLFASAKNLYDAILLSGILTVDDNSTKAPLSASMVKRYEEHQKDLKKFEDFIKVN-ALDQYNAIFKDKNK
356


WP_037593752
279
LLGEIGDEYADLFASAKNLYDAILLSGILAVDDNTTKAPLSASMVKRYEEHQKDLKKLKDFIKVN-APDQYNAIFKDKNK
357


WP_049516684
279
LLGEIGDEYADLFASAKNLYDAILLSGILAVDDNTTKAPLSASMVKRYEEHQKDLKKLKDFIKVN-APAQYDDIFKDETK
357


GAD46167
278
LLGEIGDEYADLFASAKNLYDAILLSGILAVDDNTTKAPLSASMVKRYEEHQKDLKKLKDFIKVN-APDQYNAIFKDKNK
356


WP_018363470
279
LLGKIGDDYADLFTSSKNLYDAILLSGILTVDDNSTKAPLSASMIKRYVEHHEDLEKLKEFIKAN-KSELYHDIFKDKTQ
357


WP_003043819
278
LLGQIGDQYADLFSAAKNLSDAILLSDILRSNSEVTKAPLSASMVKRYDEHHQDLALLKTLVRQQ-FPEKYAEIFKDDTK
356


WP_006269658
278
FLGEVGDEYADLFASAKNLYDAILLSGILTVDDNSTKAPLSASMVKRYEEHQKDLKKLKDFIKVN-APDQYNAIFKDKNK
356


WP_048800889
278
LLGKIGDDYADLFTSAKNLYDTILLSGILAVDDNSTKALLSASMIKRYEEHQKDLKKLKDFIKVN-APAQYDDIFKDETK
356


WP_012767106
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_014612333
278
LLAQIGNQYADLFLAAKNLSDAILLSDILRVNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_015017095
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_015057649
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_048327215
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_049519324
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNSEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_012515931
278
LLAQIGDQYADLFLAAKNLSDAILLSDILTESDEITRAPLSASMVKRYREHHKDLVTLKTLIKDQ-LPEKYQEIFLDKTK
356


WP_021320964
278
LLAQIGDQYADLFLAAKNLSDAILLSDILTESDEITRAPLSASMVKRYREHHKDLVTLKTLIKDQ-LPEKYQEIFLDKTK
356


WP_037581760
278
LLAQIGDQYADLFLAAKNLSDAILLSDILTESDEITRAPLSASMVKRYREHHKDLVTLKTLIKDQ-LPEKYQEIFLDKTK
356


WP_004232481
278
LLGKIGDDYADLFTAAKNLYDAILLSGILTVDDNSTKAPLSASMIKRYEEHHEDLEKLKTFIKVN-NFDKYHEIFKDKSK
356


WP_009854540
279
LLGKIGDDYADLFTSAKNLYDAILLSGILTVDDNSTKAPLSASMIKRYVEHHEDLEKLKEFIKAN-KSELYHDIFKDKNK
357


WP_012962174
279
LIGKIGDEYADLFTSAKNLYDAILLSGILTVADNTTKAPLSASMIKRYNEHQVDLKKLKEFIKNN-ASDKYDEIFNDKDK
357


WP_039695303
279
LLGKIGDDYADLFTSAKNLYDAILLSGILTVDDNSTKAPLSASMIKRYVEHHEDLEKLKEFIKAN-KSELYHDIFKDKNK
357


WP_014334983
278
LLGKVGDDYADLFISAKNLYDAILLSGILTVDDNSTKAPLSASMIKRYVEHHEDLEKLKEFIKIN-KLKLYHDIFKDKTK
356


WP_003099269
278
LLAQIGDQYADLFIAAKKLSDAILLSDIITVKGASTKAPLSASMVQRYEEHQQDLALLKNLVKKQ-IPEKYKEIFDNKEK
356


AHY15608
278
LLAQIGDQYADLFIAAKKLSDAILLSDIITVKGASTKAPLSASMVQRYEEHQQDLALLKNLVKKQ-IPEKYKEIFDNKEK
356


AHY17476
278
LLAQIGDQYADLFIAAKKLSDAILLSDIITVKGASTKAPLSASMVQRYEEHQQDLALLKNLVKKQ-IPEKYKEIFDNKEK
356


ESR09100

--------------------------------------------------------------------------------



AGM98575
278
LLAQIGDQYADLFIAAKKLSDAILLSDIITVKGASTKAPLSASMVQRYEEHQQDLALLKNLVKKQ-IPEKYKEIFDNKEK
356


ALF27331
278
LLAQIEDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_018372492
276
LLSKIDEEYAALFDLAKKVYDAVLLSNILTVKEKNTKAPLSASMIKRYEEHKDDLKAFKRFFRER-LPEKYETMFKDLTK
354


WP_045618028
279
LLVQIGDDFADLFLVAKKLYDAILLSGILTVTDPSTKAPLSASMIDRYENHQKDLAALKQFIKTN-LPEKYDEVFSDQSK
357


WP_045635197
278
LLGQIGDDFTDLFVSAKKLYDAILLSGILTVTDPSTKAPLSASMIERYENHQNDLAALKQFIKNN-LPEKYDEVFSDQSK
356


WP_002263549
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVGTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002263887
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVGTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002264920
278
LLGKIGDDYADLFTLAKNLYDAILLSGILTADDSSTKAPLSASMIKRYAEHHEDLEKLKEFIKAN-KPELYHDIFKDETK
356


WP_002269043
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002269448
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002271977
278
LLGKIGDDYADLFTLAKNLYDAILLSGILTADDSSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002272766
278
LLGKIGDDYADLFTLAKNLYDAILLSGILTADDSSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002273241
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002275430
278
LLTQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002276448
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002277050
278
LLGKIGDDYADLFTLAKNLYDAILLSGILTADDSSTKAPLSASMIKRYAEHHEDLEKLKEFIKAN-KPELYHDIFKDETK
356


WP_002277364
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002279025
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTADDSSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002279859
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002280230
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002281696
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002282247
278
LLGKIGDDYADLFTLAKNLYDAILLSGILTADDSSTKAPLSASMIKRYAEHHEDLEKLKEFIKAN-KPELYHDIFKDETK
356


WP_002282906
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVGTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002283846
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002287255
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002288990
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002289641
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLTQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002290427
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002295753
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002296423
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002304487
278
LLGEIGDEYADLFASAKNLYDAILLSGILAVDDNTTKAPLSASMVKRYKEHKEELAAFKRFIKEK-LPKKYEEIFKDDTK
356


WP_002305844
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002307203
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002310390
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_002352408
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_012997688
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_014677909
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_019312892
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_019313659
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVGTQAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_019314093
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_019315370
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLTQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_019803776
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVGTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_019805234
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_024783594
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVGTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_024784288
278
LLGKIGDDYADLFTLAKNLYDAILLSGILTADDSSTKAPLSASMIKRYAEHHEDLEKLKEFIKAN-KPELYHDIFKDETK
356


WP_024784666
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLVQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_024784894
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLTQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_024786433
278
LLGKIGDDYADLFTLAKNLYDAILLSGILTADDSSTKAPLSASMIKRYAEHHEDLEKLKEFIKAN-KPELYHDIFKDETK
356


WP_049473442
278
LLGKIGDDYADLFTLAKNLYDAILLSGILTADDSSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
356


WP_049474547
278
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLTQLKQFIRQK-LSDKYNEVFSDVSK
356


EMC03581
271
LLAQIGDNYAELFLSAKKLYDSILLSGILTVTDVSTKAPLSASMIQRYNEHQMDLAQLKQFIRQK-LSDKYNEVFSDVSK
349


WP_000428612
279
LLGQIGDDFADLFVAAKKLYDAILLSGILTVTDPSTKAPLSASMIERYENHQKDLATLKQFIKTN-LPEKYDEVFSDQSK
357


WP_000428613
279
LLGQIGDDFADLFLVAKKLYDAILLSGILTVTDPSTKAPLSASMIERYENHQKDLAVLKQFIKNN-LPEKYDEVFSDQSK
357


WP_049523028
278
LLGQIGDVYADLFVVAKKLYDAILLAGILSVKDPGTKAPLSASMIERYDNHQNDLSALKQFVRRN-LPEKYAEVFSDDSK
356


WP_003107102
247
LLAQIGDQYADLFIAAKNLSDAILLSDILTVKGVNTKAPLSASMVQRFNEHQDDLKLLKKLVKVQ-LPEKYKEIFDIKDK
325


WP_054279288
280
LLTQIGDEYADLFLSAKNLSDAILLSDILTVNGDGTQAPLSASLIKRYEEHRQDLALLKQMFKEQ-LPDLYRDVFTDENK
358


WP_049531101
279
LLGQIGDDFADLFLVAKKLYDAILLSGILTVTDPSTKAPLSASMIERYENHQKDLAALKQFIKNN-LPEKYDEVFSDQSK
357


WP_049538452
279
LLGQIGDGFADLFLVAKKLYDAILLSGILTVTDPSTKAPLSASMIERYQNHQNDLASLKQFIKNN-LPEKYDEVFSDQSK
357


WP_049549711
279
LLGQIGDDFADLFLVAKKLYDAILLSGILTVTDPSTKAPLSASMIERYENHQKDLTTLKQFIKNN-LPEKYDEVFSDQSK
357


WP_007896501
280
LLAEIGDHYADLFLAAKNLSDAILLSDILTLSDENTRAPLSASMIKRYEEHQEDLALLKKLVKEQ-MPEKYWEIFSNAKK
358


EFR44625
232
LLAEIGDHYADLFLAAKNLSDAILLSDILTLSDENTRAPLSASMIKRYEEHQEDLALLKKLVKEQ-MPEKYWEIFSNAKK
310


WP_002897477
278
LLGQIGDDFADLFLIAKKLYDAILLSGILTVTDPSTKAPLSASMIERYENHQKDLAALKQFIKNN-LPEKYVEVFSDQSK
356


WP_002906454
278
LLGQIGDGFADLFLVAKKLYDAILLSGILTVTDPSTKAPLSASMIERYENHQEDLAALKQFIKNN-LSEKYAEVFSDQSK
356


WP_009729476
279
LLGQIGDDFADLFLVAKKLYDAILLSGILTVTNPSTKAPLSASMIERYENHQKDLASLKQFIKNN-LPEKYDEVFSDQSE
357


CQR24647
278
LLGIIGDEYADVFVAAKKVYDSILLSGILTTNNHSTKAPLSASMIDRYDEHNSDKKLLRDFIRTNiGKEVFKEVFYDTSK
357


WP_000066813
279
LLGQIGDDFADLFLVAKKLYDAILLSGILTVKDLSTKAPLSASMIERYENHQKDLAALKQFIQNN-LQEKYDEVFSDQSK
357


WP_009754323
279
LLGQIGDDFADLFLVAKKLYDAILLSGILTVTDPSTKAPLSASMIERYENHQEDLAALKQFIKNN-LPEKYAEVFSDQSK
357


WP_044674937
278
LLGKIGDDYADLFIATKSLYDGILLAGILSTTDSTTKAPLSSSMVNRYEEHKKDLALLKNFIHQN-LSDSYKEVENDKLK
356


WP_044676715
278
LLGKIGDDYADLFIATKSLYDGILLAGILSTTDSTTKAPLSSSMVNRYEEHQKDLALLKNFIHQN-LSDSYKEVENDKLK
356


WP_044680361
278
LLGKIGDDYADLFIATKSLYDGILLAGILSTTDSTTKAPLSSSMVNRYEEHQKDLALLKNFIHQN-LSDSYKEVENDKLK
356


WP_044681799
278
LLGKIGDDYADLFIATKSLYDGILLAGILSTTDSTTKAPLSSSMVNRYEEHKKDLALLKNFIHQN-LSDSYKEVENDKLK
356


WP_049533112
278
LLGEIGDEYADLFASAKNLYDAILLSGILTVDDNSTKAPLSASMVKRYEEHQKDLKKLKDFIKVN-APDQYNAIFKDKNK
356


WP_029090905
244
LADVLADEEYDLLLTAQKIYSAIILDESMDGYEYFA-----EAKKESYRKHQEELVLVKKMLKSNaITNDERAKF---EY
315


WP_006506696
284
VEKDLGE-YVEFVDALHNVYSWVELQTIMGATHTD-NASISEAMVSRYNKHHDDLKLLKDCIKNN-VPNKYFDMFRNDSE
360


AIT42264
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_034440723
284
LLSNIDEGYRDVFLQAKNVYNAIELSKILKTDGKETKAPLSAQMVELYNQHREDLKKYKDYIKAY-LPEKYGETFKDATK
362


AKQ21048
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


WP_004636532
277
LLGMTDDVFLDVFMAAKNVYDAVEMSAIISTDTGNSKAVLSNQMINFYDEHKVDLAQLKQFFKTH-LPDKYYECFSDPSK
355


WP_002364836
284
ILAKVGDEYSDVFLAAKNVYDAVELSTILADSDKKSHAKLSSSMIVRFTEHQEDLKKFKRFIREN-CPDEYDNLFKNEQK
362


WP_016631044
235
ILAKVGDEYSDVFLAAKNVYDAVELSTILADSDKKSHAKLSSSMIVRFTEHQEDLKKFKRFIREN-CPDEYDNLFKNEQK
313


EMS75795
21
LLEKSGEEFRDVFLQAKKVYDAILLSDILSTKKQNSKAKLSLGMIERYDSHKKDLEELKQFVKAN-LPEKTAIFFKDSSK
99


WP_002373311
284
ILAKVGDEYSDVFLAAKNVYDAVELSTILADSDKKSHAKLSSSMIVRFTEHQEDLKKFKRFIREN-CPDEYDNLFKNEQK
362


WP_002378009
284
ILAKVGDEYSDVFLAAKNVYDAVELSTILADSDKKSHAKLSSSMIVRFTEHQEDLKNFKRFIREN-CPDEYDNLFKNEQK
362


WP_002407324
284
ILAKVGDEYSDVFLAAKNVYDAVELSTILADSDKKSHAKLSSSMIVRFTEHQEDLKNFKRFIREN-CPDEYDNLFKNEQK
362


WP_002413717
284
ILAKVGDEYSDVFLAAKNVYDAVELSTILADSDKKSHAKLSSSMIVRFTEHQEDLKKFKRFIREN-CPDEYDNLFKNEQK
362


WP_010775580
286
ILAKVGDEYSDVFLAAKNVYDAVELSTILADSDKKSHAKLSSSMIVRFTEHQEDLKNFKRFIREN-CPDEYDNLFKNEQK
364


WP_010818269
284
ILAKVGDEYSDVFLAAKNVYDAVELSTILADSDKKSHAKLSSSMIVRFTEHQEDLKKFKRFIREN-CPDEYDNLFKNEQK
362


WP_010824395
284
ILAKVGDEYSDVFLAAKNVYDAVELSTILADSDKKSHAKLSSSMIVRFTEHQEDLKNFKRFIREN-CPDEYDNLFKNEQK
362


WP_016622645
284
ILAKVGDEYSDVFLAAKNVYDAVELSTILADSDKKSYAKLSSSMIVRFTEHQEDLKKFKRFIREN-CPDEYDNLFKNEQK
362


WP_033624816
284
ILAKVGDEYSDVFLAAKNVYDAVELSTILADSDKKSHAKLSSSMIVRFTEHQEDLKNFKRFIREN-CPDEYDNLFKNEQK
362


WP_033625576
284
ILAKVGDEYSDVFLAAKNVYDAVELSTILADSDKKSHAKLSSSMIVRFTEHQEDLKKFKRFIREN-CPDEYDNLFKNEQK
362


WP_033789179
284
ILAKVGDEYSDVFLAAKNVYDAVELSTILADSDKKSHAKLSSSMIVRFTEHQEDLKNFKRFIREN-CPDEYDNLFKNEQK
362


WP_002310644
282
LLEKIGDDYIDLFVQAKNVYDAVLLSEILSDSTKNTRAKLSAGMIRRYDAHKEDLVLLKRFVKEN-LPKKYRAFFGDNSV
360


WP_002312694
283
LLEKIGDDYIDLFVQAKNVYDAVLLSEILSDSTKNTRAKLSAGMIRRYDAHKEDLVLLKRFVKEN-LPKKYRAFFGDNSV
361


WP_002314015
283
LLEKIGDDYIDLFVQAKNVYDAVLLSEILSDSTKNTRAKLSAGMIRRYDAHKEDLVLLKRFVKEN-LPKKYRAFFGDNSV
361


WP_002320716
283
LLEKIGDDYIDLFVQAKNVYDAVLLSEILSDSTKNTRAKLSAGMIRRYDAHKEDLVLLKRFVKEN-LPKKYRAFFGDNSV
361


WP_002330729
282
LLEKIGDDYIDLFVQAKNVYDAVLLSEILSDSTKNTRAKLSAGMIRRYDAHKEDLVLLKRFVKEN-LPKKYRAFFGDNSV
360


WP_002335161
283
LLEKIGDDYIDLFVQAKNVYDAVLLSEILSDSTKNTRAKLSAGMIRRYDAHKEDLVLLKRFVKEN-LPKKYRAFFGDNSV
361


WP_002345439
283
LLEKIGDDYIDLFVQAKNVYDAVLLSEILSDSTKNTRAKLSAGMIRRYDAHKEDLVLLKRFVKEN-LPKKYRAFFGDNSV
361


WP_034867970
276
LLEKIGDEYLDIFLQAKKVHDAILLSEIISSTVKHTKAKLSSGMVERYERHKADLAKFKQFVKEN-VPQKATVFFKDTTK
354


WP_047937432
283
LLEKIGDDYIDLFVQAKNVYDAVLLSEILSDSTKNTRAKLSAGMIRRYDAHKEDLVLLKRFVKEN-LPKKYRAFFGDNSV
361


WP_010720994
276
LLEKIGDEYLDIFLQAKKVHDAILLSEIISSTVKHTQAKLSSGMVERYERHKADLAKFKQFVKEN-VPQKATVFFKDTTK
354


WP_010737004
276
LLEKIGDEYLDIFLQAKKVHDAILLSEIISSTVKHTKAKLSSGMVERYERHKADLAKFKQFVKEN-VPQKATVFFKDTTK
354


WP_034700478
276
LLEKIGDEYLDIFLQAKKVHDAILLSEIISSTVKHTQAKLSSGMVERYERHKADLAKFKQFVKEN-VPQKATVFFKDTTK
354


WP_007209003
281
LLAIIGDEYGDIFVAAQNLYQAILLAGILTSTEK-TRAKLSASMIQRYEEHAKDLKLLKRFVKEH-IPDKYAEIFNDATK
358


WP_023519017
276
LLEKTSDDYAELFLKAKGVYDAILLSQILSKSDDETKAKLSANMKLRFEEHQRDLKQLKELVRRD-LPKKYDDFFKNRSK
354


WP_010770040
279
LLAIIGDEYAEIFSATKSVYDAVALSGILSVTDGDTKAKLSASMVERYEAHQKDLVQFKQFIRKE-LPEMYAPIFRDNSV
357


WP_048604708
275
LLGEIGDEYADVFEAAKNVYNAVELSGILTVTDNSTKAKLSASMIKRYEDHKTDLKLFKEFIRKN-LPEKYHEIFNDKNT
353


WP_010750235
276
LLRKSNEEMIDVFLQVKKVYDAILLSDILSTKMKDTKAKLSAGMIERYQNHKKDLEELKQFVRAH-LHEKVTVFFKDSSK
354


AII16583
317
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
395


WP_029073316
290
KQPLLGD-CVEFIDLLHDIYSWVELQNILGSAHTS-EPSISAAMIQRYEDHKNDLKLLKDVIRKY-LPKKYFEVFRDEKS
366


WP_031589969
290
KQPLLGD-CVEFIDLLHDIYSWVELQNILGSAHTS-EPSISAAMIQRYEDHKNDLKLLKDVIRKY-LPKKYFEVFRDEKS
366


KDA45870
276
LLAEAGDQYLDIFVAAKKVYDAAILASILDVKDTQTKTVFSQAMIERYEEHQKDLIELKRVFKKY-LPEKCHDFFSE-PK
353


WP_039099354
286
LESSLDDNAHQIIESLQELYSGVLLAGIVPENQSLS-----QAMITKYDDHQKHLKMLKAVREAL-APEDRQRLKQAYDQ
359


AKP02966
279
LDSILDDDQFTVLDTANRIYSTITLNEIL-----NGESYFSMAKVNQYENHAIDLCKLRDMWHTT----KNEKAV-GLSR
348


WP_010991369
284
LLALIGDEYAELFVAAKNAYSAVVLSSIITVAETETNAKLSASMIERFDTHEEDLGELKAFIKLH-LPKHYEEIFSNTEK
362


WP_033838504
284
LLALIGDEYAELFVAAKNAYSAVVLSSIITVAETETNAKLSASMIERFDTHEEDLGELKAFIKLH-LPKHYEEIFSNTEK
362


EHN60060
287
LLALIGDEYAELFVAAKNAYSAVVLSSIITVAETETNAKLSASMIERFDTHEEDLGELKAFIKLH-LPKHYEEIFSNTEK
365


EFR89594
53
LLALIGDEYAELFVAAKNAYSAVVLSSIITVAETETNAKLSASMIERFDTHEEDLGELKAFIKLH-LPKHYEEIFSNTEK
131


WP_038409211
284
LLAKIGDEYAEIFVAAKSTYNAVVLSNIITVTDTETKAKLSASMIERFDKHAKDLKRLKAFFKMQ-LPEKFNEVFNDIEK
362


EFR95520

--------------------------------------------------------------------------------



WP_003723650
284
LLAIIGDEYAELFVAAKNTYNAVVLSSIITVTDTETNAKLSASMIERFDAHEKDLVELKAFIKLN-LPKQYEEIFSNAAI
362


WP_003727705
284
LLAIIGDEYAELFVAAKNTYNAVVLSSIITVTATETNAKLSASMIERFDAHEKELGELKAFIKLH-LPKQYQEIFNNAEI
362


WP_003730785
284
LLAIIGDEYAELFVAAKNTYNAVVLSSIITVTATETNAKLSASMIERFDAHEKELGELKAFIKLH-LPKQYQEIFNNAEI
362


WP_003733029
284
LLAIIGDEFAEVFVAAKNAYNAVVLSNIITVTDSTTRAKLSASLIERFENHKEDLKKMKRFVRTY-LPEKYDEIFDDTEK
362


WP_003739838
284
LLAIIGDEYAELFVAAKNTYNAVVLSSIITVTDTETNAKLSASMIERFDAHEKDLSELKAFIKLH-LPKQYEEIFSNVAI
362


WP_014601172
284
LLAIIGDEYAELFVAAKNTYNAVVLSSIITVTATETNAKLSASMIERFDAHEKDLGELKAFIKLH-LPKQYQEIFNNAAI
362


WP_023548323
284
LLAIIGDEYAELFVAAKNTYNAVVLSSIITVTDTETNAKLSASMIERFDAHEKDLVELKAFIKLN-LPKQYEEIFSNAAI
362


WP_031665337
284
LLAIIGDEYAELFVAAKNTYNAVVLSSIITVNDTETNAKLSASMIERFDAHEKDLVELKAFIKLN-LPKQYEEIFSNAAI
362


WP_031669209
284
LLAIIGDEFAEVFVAAKNAYNAVVLSNIITVTDSTTRAKLSASLIERFENHKEDLKKMKRFVRTY-LPEKYDEIFDDTEK
362


WP_033920898
284
LLAIIGDEYAELFVAAKNTYNAVVLSSIITVTDTETNAKLSASMIERFDAHEKDLVELKAFIKLN-LPKQYEEIFSNAAI
362


AKI42028
287
LLAIIGDEYAELFVAAKNTYNAVVLSSIITVTATETNAKLSASMIERFDAHEKDLGELKAFIKLH-LPKQYQEIFNNAAI
365


AKI50529
287
LLAIIGDEYAELFVAAKNTYNAVVLSSIITVTDTETNAKLSASMIERFDAHEKDLVELKAFIKLN-LPKQYEEIFSNAAI
365


EFR83390

--------------------------------------------------------------------------------



WP_046323366
284
LLARVGDEYAEIFVAAKNAYNAVVLSSIITVSNTETKAKLSASMIERFDKHDKDLKRMKAFFKVR-LPENFNEVFNDVEK
362


AKE81011
294
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
372


CUO82355
288
VENDLGE-YVEFIDSLHNIYSWVELQTIMGATHTD-NASISEAMVSRYNKHHEDLQLLKKCIKDN-VPKKYFDMFRNDSE
364


WP_033162887
289
LQSELGE-YIEFIEMLHNIYSWVELQAILGATHTD-NPSISAAMVERYEEHKKDLRVLKKVIREE-LPDKYNEVFRKDNR
365


AGZ01981
311
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
389


AKA60242
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


AKS40380
278
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
356


4UN5_B
282
LLAQIGDQYADLFLAAKNLSDAILLSDILRVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQ-LPEKYKEIFFDQSK
360


WP_010922251
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLv--KLNREDLLRKQRTFDNGcustom character IPHQIHLGEL
419


WP_039695303
358
--NGYAG YIEN G VKQDEFYKYLKNILSK-IkiDGSDYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
422


WP_045635197
357
--DGYAG YIDG K TTQETFYKYIKNLLSK-F--EGTDYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


5AXW_A
169
------G SINR - ---------------K------TSDYVk----------------------------EA
183


WP_009880683
41
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLRKQRTFDNGSIPHQIHLGEL
103


WP_010922251
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLv--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


WP_011054416
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLRKQRTFDNGSIPYQIHLGEL
419


WP_011284745
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


WP_011285506
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLv--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


WP_011527619
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


WP_012560673
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


WP_014407541
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLv--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


WP_020905136
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


WP_023080005
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLRKQRTFDNGSIPYQIHLGEL
419


WP_023610282
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLRKQRTFDNGSIPYQIHLGEL
419


WP_030125963
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLv--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


WP_030126706
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLRKQRTFDNGSIPYQIHLGEL
419


WP_031488318
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


WP_032460140
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


WP_032461047
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


WP_032462016
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLv--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


WP_032462936
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


WP_032464890
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNRKDLLRKQRTFDNGSIPHQIHLGEL
419


WP_033888930
182
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLv--KLNREDLLRKQRTFDNGSIPHQIHLGEL
244


WP_038431314
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


WP_038432938
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLRKQRTFDNGSIPYQIHLGEL
419


WP_038434062
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


BAQ51233
268
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLv--KLNREDLLRKQRTFDNGSIPHQIHLGEL
330


KGE60162

------- ---- - ----------------------------------------------------------



KGE60856

------- ---- - ----------------------------------------------------------



WP_002989955
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


WP_003030002
357
--KGYAG YIEN G VKQDEFYKYLKGILLQ-I--NGSGDFL--DKIDREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_003065552
360
--NGYAG YIEN G VKQDEFYKYLKNTLSK-Ia--GSDYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
422


WP_001040076
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EGSEYFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040078
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EDSENFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040080
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EDSENFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040081
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EDSENFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040083
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EDSENFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040085
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EDSENFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040087
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EDSENFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040088
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EDSENFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040089
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EDSENFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040090
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EDSENFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040091
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EDSENFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040092
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EDSEYFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040094
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EGSEYLL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040095
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EGSEYLL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040096
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EGSEYLL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040097
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EGSEYLL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040098
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EGSEYLL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040099
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EGSEYLL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040100
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EGSEYLL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040104
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EDSENFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040105
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EDSENFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040106
358
--DGYAG YIEG K TNQGAFYKYLSKLLTK-Q--EGSEYFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040107
358
--DGYAG YIEG K TNQGAFYKYLSKLLTK-Q--EGSEYFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040108
358
--DGYAG YIEG K TNQGAFYKYLSKLLTK-Q--EGSEYFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040109
358
--DGYAG YIEG K TNQGAFYKYLSKLLTK-Q--EGSEYFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_001040110
358
--DGYAG YIEG K TNQGAFYKYLSKLLTK-Q--EGSEYFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_015058523
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EDSEYFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_017643650
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EGSEYLL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_017647151
358
--DGYAG YIEG K TNQGAFYKYLSKLLTK-Q--EGSEYFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_017648376
358
--DGYAG YIEG K TNQGAFYKYLSKLLTK-Q--EGSEYFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_017649527
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EDSENFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_017771611
358
--DGYAG YIEG K TNQGAFYKYLSKLLTK-Q--EGSEYFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


WP_017771984
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EDSENFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


CFQ25032
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EDSENFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


CFV16040
358
--DGYAG YIEG K TNQEAFYKYLSKLLTK-Q--EDSENFL--EKIKNEDFLRKQRTFDNGSIPHQVHLTEL
420


KLJ37842
358
--DGYAG YIEG K TNQEAFYKYLSELLTK-Q--EDSENFL--EKIKNEDFLREQRTEDNGSIPHQVHLTEL
420


KLJ72361
358
--DGYAG YIEG K TNQEAFYKYLSELLTK-Q--EDSENFL--EKIKNEDFLREQRTEDNGSIPHQVHLTEL
420


ELL20707
358
--DGYAG YIEG K TNQEAFYKYLSELLTK-Q--EDSENFL--EKIKNEDFLREQRTEDNGSIPHQVHLTEL
420


KLL42645
358
--DGYAG YIEG K TNQGAFYKYLSELLTK-Q--EGSEYFL--EKIKNEDFLREQRTEDNGSIPHQVHLTEL
420


WP_047207273
358
--DGYAG YIEG K TNQEAFYKYLSELLTK-Q--EDSENFL--EKIKNEDFLREQRTEDNGSIPHQVHLTEL
420


WP_047209694
358
--DGYAG YIEG K TNQEAFYKYLSELLTK-Q--EGSEYLL--EKIKNEDFLREQRTEDNGSIPHQVHLTEL
420


WP_050198062
358
--DGYAG YIEG K TNQEAFYKYLSELLTK-Q--EDSENFL--EKIKNEDFLREQRTEDNGSIPHQVHLTEL
420


WP_050201642
358
--DGYAG YIEG K TNQEAFYKYLSELLTK-Q--EDSENFL--EKIKNEDFLREQRTEDNGSIPHQVHLTEL
420


WP_050204027
358
--DGYAG YIES K TNQGAFYKYLSELLTK-Q--EGSEYFL--EKIKNEDFLREQRTEDNGSIPHQVHLTEL
420


WP_050881965
358
--DGYAG YIEG K TNQEAFYKYLSELLTK-Q--EDSENFL--EKIKNEDFLREQRTEDNGSIPHQVHLTEL
420


WP_050886065
358
--DGYAG YIEG K TNQEAFYKYLSELLTK-Q--EDSENFL--EKIKNEDFLREQRTEDNGSIPHQVHLTEL
420


AHN30376
358
--DGYAG YIEG K TNQEAFYKYLSELLTK-Q--EDSEYFL--EKIKNEDFLREQRTEDNGSIPHQVHLTEL
420


EA078426
358
--DGYAG YIEG K TNQEAFYKYLSELLTK-Q--EDSENFL--EKIKNEDFLREQRTEDNGSIPHQVHLTEL
420


CCW42055
358
--DGYAG YIEG K TNQEAFYKYLSELLTK-Q--EGSEYLL--EKIKNEDFLREQRTEDNGSIPHQVHLTEL
420


WP_003041502
357
--KGYAG YIES G VKQDEFYKYLEGILLQ-I--NGSGDFL--DKIDREDFLREQRTEDNGSIPHQIHLQEM
419


WP_037593752
358
--KGYAG YIES G VEQDEFYKYLEGILLK-I--NGSGDFL--DKIDCEDFLREQRTEDNGSIPHQIHLQEM
420


WP_049516684
358
--NGYAG YIEN G VKQDEFYKYLENTLSK-I--DGSDYFL--DKIDREDFLREQRTEDNGSIPHQIHLQEM
420


GAD46167
357
--KGYAG YIES G VEQDEFYKYLEGILLK-I--NGSGDFL--DKIDCEDFLREQRTEDNGSIPHQIHLQEM
419


WP_018363470
358
--NGYAG YIEN G VKQDEFYKYLEGILTK-I--NGSDYFL--DKIEREDFLREQRTEDNGSIPHQIHLQEM
420


WP_003043819
357
--NGYAG YVGI G ATQEEFYKFIKPILEK-M--DGAEELLa--KLNRDDLLREQRTEDNGSIPHQIHLKEL
429


WP_006269658
357
--KGYAS YIES G VKQDEFYKYLEGILLK-I--NGSGDFL--DKIDREDFLREQRTEDNGSIPHQIHLQEM
419


WP_048800889
357
--NGYAG YIEN G VKQDEFYKYLENTLSK-I--DGSGYFL--DKIEREDFLREQRTEDNGSIPHQIHLQEM
419


WP_012767106
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLREQRTEDNGSIPHQIHLGEL
419


WP_014612333
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLREQRTEDNGSIPHQIHLGEL
419


WP_015017095
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLREQRTEDNGSIPHQIHLGEL
419


WP_015057649
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLREQRTEDNGSIPHQIHLGEL
419


WP_048327215
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLREQRTEDNGSIPHQIHLGEL
419


WP_049519324
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLa--KLNREDLLREQRTEDNGSIPHQIHLGEL
419


WP_012515931
357
--NGYAG YIEG Q VSQEEFYKYLKPILAR-L--DGSEPLL1--KIDREDFLREQRTEDNGSIPHQIHLEEL
419


WP_021320964
357
--NGYAG YIEG Q VSQEEFYKYLKPILAR-L--DGSEPLL1--KIDREDFLREQRTEDNGSIPHQIHLEEL
419


WP_037581760
357
--NGYAG YIEG Q VSQEEFYKYLKPILAR-L--DGSEPLL1--KIDREDFLREQRTEDNGSIPHQIHLEEL
419


WP_004232481
357
--NGYAG YIEN G VKQDIFYKHLKSIISE-K--NGGQYFL--DKIEREDFLREQRTEDNGSIPYQIHLQEM
419


WP_009854540
358
--NGYAG YIEN G VKQDEFYKYLENTLSK-I--DGSDYFL--DKIEREDFLREQRTEDNGSIPHQIHLQEM
420


WP_012962174
358
--NGYAG YIEN G VKQDEFYKYLETTLSK-I--DGSDYFL--DKIEREDFLREQRTEDNGSIPHQIHLQEM
420


WP_039695303
358
--NGYAG YIEN G VKQDEFYKYLKNILSK-IkiDGSDYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
422


WP_014334983
357
--NGYAG YIDN G VKQDEFYKYLKTILTK-I--DDSDYFL--DKIERDDFLRKQRTFDNGSIPHQIHLQEM
419


WP_003099269
357
--NGYAG YIDG K TSQEEFYKYIKPILLK-L--DGTEKLIs--KLEREDFLRKQRTFDNGSIPHQIHLNEL
419


AHY15608
357
--NGYAG YIDG K TSQEEFYKYIKPILLK-L--DGTEKLIs--KLEREDFLRKQRTFDNGSIPHQIHLNEL
419


AHY17476
357
--NGYAG YIDG K TSQEEFYKYIKPILLK-L--DGTEKLIs--KLEREDFLRKQRTFDNGSIPHQIHLNEL
419


ESR09100

------- ---- - ----------------------------------------------------------



AGM98575
357
--NGYAG YIDG K TSQEEFYKYIKPILLK-L--DGTEKLIs--KLEREDFLRKQRTFDNGSIPHQIHLNEL
419


ALF27331
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_018372492
355
--PSYAA YVSG A VTEDDFYKFSKGLLID-V--EGAEYFL--EKIEREDFLRKQRTFDNGAIPNQVHVKEL
432


WP_045618028
358
--DGYAG YIDG K TTQEAFYKYIKNLLSK-L--EGADYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
420


WP_045635197
357
--DGYAG YIDG K TTQETFYKYIKNLLSK-F--EGTDYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002263549
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002263887
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002264920
357
--NGYAG YIEN G VKQDEFYKYLKNTLSK-I--AGSDYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002269043
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002269448
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002271977
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002272766
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002273241
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002275430
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002276448
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002277050
357
--NGYAG YIEN G VKQDEFYKYLKNTLSK-I--AGSDYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002277364
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002279025
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002279859
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002280230
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002281696
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002282247
357
--NGYAG YIEN G VKQDEFYKYLKNTLSK-I--TGSDYFL--DQIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002282906
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002283846
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002287255
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002288990
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002289641
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002290427
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002295753
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002296423
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002304487
357
--NGYAG YVGA D ATEEEFYKYVKGILNK-V--EGADVWL--DKIDREDFLRKQRTFDNGSIPHQIHLQEM
429


WP_002305844
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002307203
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002310390
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002352408
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_012997688
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_014677909
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_019312892
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_019313659
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_019314093
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_019315370
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGNGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_019803776
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_019805234
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_024783594
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_024784288
357
--NGYAG YIEN G VKQDEFYKYLKNTLSK-I--TGSDYFL--DQIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_024784666
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_024784894
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_024786433
357
--NGYAG YIEN G VKQDEFYKYLKNTLSK-I--AGSDYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_049473442
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_049474547
357
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


EMC03581
350
--DGYAG YIDG K TNQEAFYKYLKGLLNK-I--EGSGYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
412


WP_000428612
358
--DGYAG YIDG K TTQESFYKYIKNLLSK-F--EGADYFL--EKIEREDFLRKQRTFDNGSIPHQIHLQEM
420


WP_000428613
358
--DGYAG YIDG K TTQEAFYKYIKNLLSK-F--EGTDYFL--EKIEREDFLRKQRTFDNGSIPHQIHLQEM
420


WP_049523028
357
--DGYAG YIDG K TTQEGFYKYIKNLISK-I--EGAEYFL--EKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_003107102
326
--NGYAG YING K TSQEDFYKYIKPILSK-L--KGAESLIs--KLEREDFLRKQRTFDNGSIPHQIHLNEL
388


WP_054279288
359
--DGYAG YISG K TSQEAFYKYIKPILET-L--DGAEDFLt--KINREDFLRKQRTFDNGSIPHQIHLGEL
421


WP_049531101
358
--EGYAG YIDS K TTQEAFYKYIKNLLSK-I--DGADYLL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
420


WP_049538452
358
--DGYAG YVDG K TTQEAFYKYIKNLLSK-F--EGADYFL--EKIEREDFLRKQRTFDNGSIPHQIHLQEM
420


WP_049549711
358
--DGYAG YIDG K TTQEAFYKYIKNLLSK-F--EGTDYFL--EKIEREDFLRKQRTFDNGSIPHQIHLQEM
420


WP_007896501
359
--NGYAG YIEG K VSQEDFYRYIKPILSR-L--KGGDEFLa--KIDRDDFLRKQRTFDNGSIPHQIHLKEL
421


EFR44625
311
--NGYAG YIEG K VSQEDFYRYIKPILSR-L--KGGDEFLa--KIDRDDFLRKQRTFDNGSIPHQIHLKEL
373


WP_002897477
357
--DGYAG YIDG K TTQEAFYKYIKNLLSK-F--EGADYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_002906454
357
--DGYAG FIDG K TTQEAFYKYIKNLLSK-L--EGADYFL--NKIEREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_009729476
358
--DGYAG YIDG K TTQETFYKYIKNLLSK-F--EGADYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
420


CQR24647
358
--NGYAG YIDG K TNQEDFYKYLKNLLQK-V--DGGDYFI--EKIEREDFLRKQRTFDNGSIPHQVHLDEM
420


WP_000066813
358
--DGYAG YIDG K TTQEAFYKYIKNLLSK-F--EGADYFL--DKIEREDFLKKQRTFDNGSIPHQIHLQEM
420


WP_009754323
358
--DGYAG YIDG K TTQEAFYKYIKNLLSK-F--EGADYFL--DKIEREDFLRKQRTFDNGSIPHQIHLQEM
420


WP_044674937
357
--DGYAG YIEG K TTQENFYRFIKKAIEK-I--EGSDYFI--DKIDREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_044676715
357
--DGYAG YIEG K TTQENFYRFIKKAIEK-I--EGSNYFI--DKIDREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_044680361
357
--DGYAG YIEG K TTQENFYRFIKKAIEK-I--EGSNYFI--DKIDREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_044681799
357
--DGYAG YIEG K TTQENFYRFIKKAIEK-I--EGSDYFI--DKIDREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_049533112
357
--KGYAG YIEN G VKQDEFYKYLKGILLQ-I--NGSGDFL--DKIDREDFLRKQRTFDNGSIPHQIHLQEM
419


WP_029090905
316
fyTDYIG YEES K SKEERLFKHIELLLAKeNv1TTVEHAL1eKNITFASLLPLQRSSRNAVIPYQVHEKEL
403


WP_006506696
361
ksKGYYN YINR K APVDEFYKYVKKCIEK-VdtPEAKQILn--DIELENFLLKQNSRTNGSVPYQMQLDEM
429


AIT42264
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLv--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


WP_034440723
363
--NGYAG YIDG K TSQEDFYKFVKAQLKG---eENGEYFL--EAIENENFLRKQRSFYNGVIPYQIHLQEL
425


AKQ21048
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLv--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


WP_004636532
356
--NGYAG YIDG K TNQEDFYKYIEKVMKT-IksDKKDYFL--DKIDREVFLRKQRSFYNSVIPHQIHLQEM
420


WP_002364836
363
--DGYAG YIAH A VSQLKFYQYVKKIIQD-I--AGAEYFL--EKIAQENFLRKQRTFDNGVIPHQIHLAEL
427


WP_016631044
314
--DGYAG YIAH A VSQLKFYQYVKKIIQD-I--AGAEYFL--EKIAQENFLRKQRTFDNGVIPHQIHLAEL
378


EMS75795
100
--NGYAG YIDG K TTQEDFYKFLKKELNG-I--AGSERFM--EKVDQENFLLKQRTTANGVIPHQVHLTEL
162


WP_002373311
363
--DGYAG YIAH A VSQLKFYQYVKKIIQD-I--AGAEYFL--EKIAQENFLRKQRTFDNGVIPHQIHLAEL
427


WP_002378009
363
--DGYAG YITH A VSQLKFYQYVKKIIQD-I--AGAEYFL--EKIAQENFLRKQRTFDNGVIPHQIHLAEL
427


WP_002407324
363
--DGYAG YITH A VSQLKFYQYVKKIIQD-I--AGAEYFL--EKIAQENFLRKQRTFDNGVIPHQIHLAEL
427


WP_002413717
363
--DGYAG YIAH A VSQLKFYQYVKKIIQD-I--AGAEYFL--EKIAQENFLRKQRTFDNGVIPHQIHLAEL
427


WP_010775580
365
--DGYAG YIAH A VSQLKFYQYVKKIIQD-I--AGAEYFL--EKIAQENFLRKQRTFDNGVIPHQIHLAEL
429


WP_010818269
363
--DGYAG YIAH A VSQLKFYQYVKKIIQD-I--AGAEYFL--EKIAQENFLRKQRTFDNGVIPHQIHLAEL
427


WP_010824395
363
--DGYAG YITH A VSQLKFYQYVKKIIQD-I--AGAEYFL--EKIAQENFLRKQRTFDNGVIPHQIHLAEL
427


WP_016622645
363
--DGYAG YIAH A VSQLKFYQYVKKIIQD-I--AGAEYFL--EKIAQENFLRKQRTFDNGVIPHQIHLAEL
427


WP_033624816
363
--DGYAG YIAH A VSQLKFYQYVKKIIQD-I--AGAEYFL--EKIAQENFLRKQRTFDNGVIPHQIHLAEL
427


WP_033625576
363
--DGYAG YIAH A VSQLKFYQYVKKIIQD-I--AGAEYFL--EKIAQENFLRKQRTFDNGVIPHQIHLAEL
427


WP_033789179
363
--DGYAG YIAH A VSQLKFYQYVKKIIQD-I--AGAEYFL--EKIAQENFLRKQRTFDNGVIPHQIHLAEL
427


WP_002310644
361
--NGYAG YIEG H ATQEDFYKFVKKELTG-I--RGSEVFL--TKIEQENFLRKQRTFDNGVIPHQIHLTEL
423


WP_002312694
362
--NGYAG YIEG H ATQEAFYKFVKKELTG-I--RGSEVFL--TKIEQENFLRKQRTFDNGVIPHQIHLSEL
424


WP_002314015
362
--NGYAG YIEG H ATQEDFYKFVKKELTG-I--RGSEVFL--TKIEQENFLRKQRTFDNGVIPHQIHLTEL
424


WP_002320716
362
--NGYAG YIEG H ATQEDFYKFVKKELTG-I--RGSEVFL--TKIEQENFLRKQRTFDNGVIPHQIHLTEL
424


WP_002330729
361
--NGYAG YIEG H ATQEDFYKFVKKELTG-I--RGSEVFL--TKIEQENFLRKQRTFDNGVIPHQIHLTEL
423


WP_002335161
362
--NGYAG YIEG H ATQEDFYKFVKKELTG-I--RGSEVFL--TKIEQENFLRKQRTFDNGVIPHQIHLTEL
424


WP_002345439
362
--NGYAG YIEG H ATQEDFYKFVKKELTG-I--RGSEVFL--TKIEQENFLRKQRTFDNGVIPHQIHLTEL
424


WP_034867970
355
--NGYAG YIKG K TTQEEFYKFVKKELSG-V--VGSEPFL--EKIDQETFLLKQRTYTNGVIPHQVHLIEL
417


WP_047937432
362
--NGYAG YIEG H ATQEDFYKFVKKELTG-I--RGSEVFL--TKIEQENFLRKQRTFDNGVIPHQIHLTEL
424


WP_010720994
355
--NGYAG YIKG K TTQEEFYKFVKKELSG-V--VGSEPFL--EKIDQETFLLKQRTYTNGVIPHQVHLIEL
417


WP_010737004
355
--NGYAG YIKG K TTQEEFYKFVKKELSG-V--VGSEPFL--EKIDQETFLLKQRTYTNGVIPHQVHLIEL
417


WP_034700478
355
--NGYAG YIKG K TTQEEFYKFVKKELSG-V--VGSEPFL--EKIDQETFLLKQRTYTNGVIPHQVHLIEL
417


WP_007209003
359
--NGYAG YIDG K TKEEEFYKYLKTTLVQ---kSGYQYFI--EKIEQENFLRKQRIYDNGVIPHQVHAEEL
421


WP_023519017
355
--NGYAG YVKG K ATQEDFYKFLRTELAG-L--EESQSIM--EKIDLEIYLLKQRTFANGVIPHQIHLVEM
417


WP_010770040
358
--SGYAG YVEN S VTQAEFYKYIKKAIEK-V--PGAEYFL--EKIEQETFLDKQRTFNNGVIPHQIHLEEL
422


WP_048604708
354
--DGYAG YIDN S TSQEKFYKYITNLIEK-I--DGAEYFL--KKIENEDFLRKQRTFDNGIIPHQIHLEEL
418


WP_010750235
355
--DGYAG YIDG K TTQADFYKFLKKELTG-V--PGSEPML--AKIDQENFLLKQRTPTNGVIPHQVHLTEF
417


AII16583
396
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLv--KLNREDLLRKQRTEDNGSIPHQIHLGEL
458


WP_029073316
367
kkNNYCN YINH K TPVDEFYKYIKKLIEK-IddPDVKTILn--KIELESFMLKQNSRTNGAVPYQMQLDEL
435


WP_031589969
367
kkNNYCN YINH K TPVDEFYKYIKKLIEK-IddPDVKTILn--KIELESFMLKQNSRTNGAVPYQMQLDEL
435


KDA45870
354
-iSGYAG YIDG K VSEEDFYKYTKKTLKG-I--PETEEILq--KIDANNYLRKQRTFDNGAIPHQVHLKEL
417


WP_039099354
360
------- YVDG K -SKEDFYGDITKALKNnPdhPIVSEIKk--LIELDQFMPKQRTKDNGAIPHQLHQQEL
425


AKP02966
349
--QAYDD YINK K ---KELYTSLKKFLKVaLp-TNLAKEAe-EKISKGTYLVKPRNSENGVVPYQLNKIEM
415


WP_010991369
363
--HGYAG YIDG - TKQADFYKYMKMTLEN-I--EGADYFI--AKIEKENFLRKQRTFDNGAIPHQLHLEEL
425


WP_033838504
363
--HGYAG YIDG - TKQADFYKYMKMTLEN-I--EGADYFI--AKIEKENFLRKQRTFDNGAIPHQLHLEEL
425


EHN60060
366
--HGYAG YIDG - TKQADFYKYMKMTLEN-I--EGADYFI--AKIEKENFLRKQRTFDNGAIPHQLHLEEL
428


EFR89594
132
--HGYAG YIDG - TKQADFYKYMKTTLEN-I--EGADYFI--AKIEKENFLRKQRTFDNGAIPHQLHLEEL
194


WP_038409211
363
--DGYAG YIDG - TTQEKFYKYMKKMLAN-I--DGADYFI--DQIEEENFLRKQRTFDNGTIPHQLHLEEL
425


EFR95520
1
------- ---- - ---------MKKMLAN-I--DGADYFI--DQIEEENFLRKQRTFDNGTIPHQLHLEEL
44


WP_003723650
363
--DGYAG YIDG - TKQVDFYKYLKTILEN-I--EGSDYFI--AKIEEENFLRKQRTFDNGAIPHQLHLEEL
425


WP_003727705
363
--DGYAG YIDG - TKQVDFYKYLKTTLEN-V--EGADYFI--TKIEEENFLRKQRTFDNGVIPHQLHLEEL
425


WP_003730785
363
--DGYAG YIDG - TKQVDFYKYLKTTLEN-V--EGADYFI--TKIEEENFLRKQRTFDNGVIPHQLHLEEL
425


WP_003733029
363
--HGYAG YISG - TKQADFYKYMKATLEK-I--EGADYFI--AKIEEENFLRKQRTFDNGVIPHQLHLEEL
425


WP_003739838
363
--DGYAG YIDG - TKQVDFYKYLKTLLEN-I--EGADYFI--AKIEEENFLRKQRTFDNGAIPHQLHLEEL
425


WP_014601172
363
--DGYAG YIDG - TKQVDFYKYLKTILEN-I--EGADYFI--AKIEEENFLRKQRTFDNGAIPHQLHLEEL
425


WP_023548323
363
--DGYAG YIDG - TKQVDFYKYLKTTLEN-V--EGADYFI--TKIEEENFLRKQRTFDNGVIPHQLHLEEL
425


WP_031665337
363
--DGYAG YIDG - TKQVDFYKYLKTILEN-I--EGSDYFI--AKIEEENFLRKQRTFDNGAIPHQLHLEEL
425


WP_031669209
363
--HGYAG YISG - TKQADFYKYMKATLEK-I--EGADYFI--AKIEEENFLRKQRTFDNGVIPHQLHLEEL
425


WP_033920898
363
--DGYAG YIDG - TKQVDFYKYLKTILEN-I--EGADYFI--AKIEEENFLRKQRTFDNGAIPHQLHLEEL
425


AKI42028
366
--DGYAG YIDG - TKQVDFYKYLKTILEN-I--EGADYFI--AKIEEENFLRKQRTFDNGAIPHQLHLEEL
428


AKI50529
366
--DGYAG YIDG - TKQVDFYKYLKTILEN-I--EGADYFI--AKIEEENFLRKQRTFDNGAIPHQLHLEEL
428


EFR83390

------- ---- - ----------------------------------------------------------



WP_046323366
363
--DGYAG YIEG - TKQEAFYKYMKKMLEH-V--EGADYFI--NQIEEENFLRKQRTFDNGAIPHQLHLEEL
425


AKE81011
373
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLv--KLNREDLLRKQRTFDNGSIPHQIHLGEL
435


CUO82355
365
kvKGYYN YINR K APVDEFYKFVKKCIEK-VdtPEAKQILh--DIELENFLLKQNSRTNGSVPYQMQLDEM
433


WP_033162887
366
klHNYLG YIKY D TPVEEFYKYIKGLLAK-VdtDEAREILe--RIDLEKFMLKQNSRTNGSIPYQMQKDEM
434


AGZ01981
390
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLv--KLNREDLLRKQRTFDNGSIPHQIHLGEL
452


AKA60242
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLv--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


AKS40380
357
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLv--KLNREDLLRKQRTFDNGSIPHQIHLGEL
419


4UN5_B
361
--NGYAG YIDG G ASQEEFYKFIKPILEK-M--DGTEELLv--KLNREDLLRKQRTFDNGSIPHQIHLGEL
423


WP_010922251
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEcustom character VVDKGA
486


WP_039695303
423
HAILRRQGDYYPFLKE--KQD RIEKILTFRIPYYVGPL VRKD--SRFAWAEY---RSDEKITPWNFDKVIDKEK
489


WP_045635197
420
NAILRRQGEYYPFLKD--NKE KIEKILTFRIPYYVGPL ARGN--RDFAWLTR---NSDEAIRPWNFEEIVDKAS
486


5AXW_A
184
KQLLKVQKAYHQLDQSfi--D TYIDLLETRRTYYEGPG ---Eg-SPFGWKDI----------------------
229


WP_009880683
104
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
170


WP_010922251
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_011054416
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_011284745
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_011285506
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_011527619
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_012560673
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_014407541
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_020905136
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_023080005
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_023610282
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_030125963
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_030126706
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_031488318
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_032460140
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_032461047
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_032462016
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_032462936
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_032464890
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_033888930
245
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
311


WP_038431314
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_038432938
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_038434062
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


BAQ51233
331
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
397


KGE60162

--------------------- ----------------- ------------------------------------



KGE60856

--------------------- ----------------- ------------------------------------



WP_002989955
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_003030002
420
HAILRRQEEHYPFLKE--NQD KIEKILTFRIPYYVGPL ARKG--SRFAWAEY---KADEKITPWNFDDILDKEK
486


WP_003065552
423
HAILRRQGDYYPFLKE--NQD RIEKILTFRIPYYVGPL ARKD--SRFSWAEY---HSDEKITPWNFDKVIDKEK
489


WP_001040076
421
RAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040078
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040080
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040081
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040083
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040085
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040087
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040088
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040089
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040090
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040091
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040092
421
KAIIRRQSEYYPFLKE--NQD KIEKILTFRIPYYVGPL ARGN--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040094
421
RAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040095
421
RAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040096
421
RAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040097
421
RAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040098
421
RAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040099
421
RAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040100
421
RAIIRRQSEYYPLLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040104
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040105
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_001040106
421
KAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEELVDKEA
487


WP_001040107
421
KAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEELVDKEA
487


WP_001040108
421
KAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEELVDKEA
487


WP_001040109
421
KAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEELVDKEA
487


WP_001040110
421
KAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEELVDKEA
487


WP_015058523
421
KAIIRRQSEYYPFLKE--NQD KIEKILTFRIPYYVGPL ARGN--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_017643650
421
RAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_017647151
421
KAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEELVDKEA
487


WP_017648376
421
KAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEELVDKEA
487


WP_017649527
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_017771611
421
KAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEELVDKEA
487


WP_017771984
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


CFQ25032
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


CFV16040
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


KLJ37842
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


KLJ72361
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


KLL20707
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


KLL42645
421
KAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEELVDKEA
487


WP_047207273
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_047209694
421
RAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_050198062
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_050201642
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_050204027
421
KAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEELVDKEA
487


WP_050881965
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


WP_050886065
421
KDIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


AHN30376
421
KAIIRRQSEYYPFLKE--NQD KIEKILTFRIPYYVGPL ARGN--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


EA078426
421
KAIIRRQSEYYPFLKE--NQD RIEKILTFRIPYYIGPL AREK--SDFAWMTR---KTDDSIRPWNFEDLVDKEK
487


CCW42055
421
RAIIRRQSEYYPFLKE--NLD RIEKILTFRIPYYVGPL AREK--SDFAWMTR---KTDDSIRPWNFEELVDKEA
487


WP_003041502
420
HAILRRQGEHYPFLKE--NQD KIEKILTFRIPYYVGPL ARKG--SRFAWAEY---KADEKITPWNFDDILDKEK
486


WP_037593752
421
HAILRRQGEHYPFLKE--NQD KIEKILTFRIPYYVGPL ARKG--SRFAWAEY---KADEKITPWNFDDILDKEK
487


WP_049516684
421
HAILRRQGEHYPFLKE--NQD KIEKILTFRIPYYVGPL ARKG--SRFAWAEY---KADEKITPWNFDDILDKEK
487


GAD46167
420
HAILRRQGEHYPFLKE--NQD KIEKILTFRIPYYVGPL ARKG--SRFAWAEY---KADEKITPWNFDDILDKEK
486


WP_018363470
421
HAILRRQGDYYPFLKE--NQE EIEKILTFRIPYYVGPL ARKD--SRFAWAEY---RSDEKITPWNFDKVIDKEK
487


WP_003043819
430
HAILRRQEEFYPFLKE--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWLTR---KSEEAITPWNFEEVVDKGA
496


WP_006269658
420
HAILRRQGEHYPFLKE--NQD KIEKILTFRIPYYVGPL ARKG--SRFAWAEY---KADEKITPWNFDDILDKEK
486


WP_048800889
420
HAILRRQGEHYPFLKE--NQD KIEKILTFRIPYYVGPL VRKG--SRFAWAEY---KADEKITPWNFDDILDKEK
486


WP_012767106
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_014612333
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_015017095
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_015057649
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_048327215
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_049519324
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_012515931
420
HAILRRQEVEYPFLKD--NRK KIESLLTFRIPYYVGPL ARG-h-SRFAWVKR---KFDGAIRPWNFEEIVDEEA
486


WP_021320964
420
HAILRRQEVEYPFLKD--NRK KIESLLTFRIPYYVGPL ARG-h-SRFAWVKR---KFDGAIRPWNFEEIVDEEA
486


WP_037581760
420
HAILRRQEVEYPFLKD--NRK KIESLLTFRIPYYVGPL ARG-h-SRFAWVKR---KFDGAIRPWNFEEIVDEEA
486


WP_004232481
420
RTILRRQGEYYPFLKE--NQA KIEKILTFRIPYYVGPL ARKN--SRFAWAKY---HSDEPITPWNFDEVVDKEK
486


WP_009854540
421
HAILRRQGDYYPFLKE--KQD RIEKILTFRIPYYVGPL VRKD--SRFAWAEY---RSDEKITPWNFDKVIDKEK
487


WP_012962174
421
HAILRRQGEHYAFLKE--NQA KIEKILTFRIPYYVGPL ARKN--SRFAWAEY---HSDEKITPWNFDEIIDKEK
487


WP_039695303
423
HAILRRQGDYYPFLKE--KQD RIEKILTFRIPYYVGPL VRKD--SRFAWAEY---RSDEKITPWNFDKVIDKEK
489


WP_014334983
420
HSILRRQGDYYPFLKE--NQA KIEKILTFRIPYYVGPL ARKD--SRFAWANY---HSDEPITPWNFDEVVDKEK
486


WP_003099269
420
KAIIRRQEKFYPFLKE--NQK KIEKLFTFKIPYYVGPL ANG-q-SSFAWLKR---QSNESITPWNFEEVVDQEA
486


AHY15608
420
KAIIRRQEKFYPFLKE--NQK KIEKLFTFKIPYYVGPL ANG-q-SSFAWLKR---QSNESITPWNFEEVVDQEA
486


AHY17476
420
KAIIRRQEKFYPFLKE--NQK KIEKLFTFKIPYYVGPL ANG-q-SSFAWLKR---QSNESITPWNFEEVVDQEA
486


ESR09100

--------------------- ----------------- ------------------------------------



AGM98575
420
KAIIRRQEKFYPFLKE--NQK KIEKLFTFKIPYYVGPL ANG-q-SSFAWLKR---QSNESITPWNFEEVVDQEA
486


ALF27331
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYIGPL ARGK--SDFSWLSR---KSADKITPWNFDEIVDKES
486


WP_018372492
433
QAIILNQSKYYPFLAE--NKE KIEKILTFRIPYYVGPL ARGN--SSFAWLQR---KSDEAIRPWNFEQVVDMET
499


WP_045618028
421
NAIIRRQGEHYPFLQE--NKE KIEKILTFRIPYYVGPL ARGN--RDFAWLTR---NSDQAIRPWNFEEIVDKAR
487


WP_045635197
420
NAILRRQGEYYPFLKD--NKE KIEKILTFRIPYYVGPL ARGN--RDFAWLTR---NSDEAIRPWNFEEIVDKAS
486


WP_002263549
420
RAIIRRQAEFYPFLAD--NQD RIEKLLTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002263887
420
RAIIRRQAEFYPFLAD--NQD RIEKLLTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002264920
420
HAILRRQGDYYPFLKE--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002269043
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002269448
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002271977
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002272766
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002273241
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002275430
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002276448
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002277050
420
HAILRRQGDYYPFLKE--NQD RIEKILTFRIPYYVGPL ARKN--SRFAWAEY---HSDEAVMPWNFDQVIDKES
486


WP_002277364
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002279025
420
RAIIRRQSEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002279859
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002280230
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002281696
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002282247
420
HAILRRQGDYYPFLKE--NQD RIEKILTFRIPYYVGPL ARKN--SRFAWAEY---HSDEAVTPWNFDQVIDKES
486


WP_002282906
420
RAIIRRQAEFYPFLAD--NQD RIEKLLTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002283846
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002287255
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002288990
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002289641
420
RAIIRRQAEFYPFLAD--NQD RIEKLLTFRIPYYVGPL ASGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002290427
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002295753
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002296423
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002304487
430
HAILRRQGEHYPFLKE--NQD KIEKILTFRIPYYVGPL VRKG--SRFAWAEY---KADEKITPWNFDDILDKEK
496


WP_002305844
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002307203
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002310390
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_002352408
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_012997688
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_014677909
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_019312892
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_019313659
420
RAIIRRQAEFYPFLAD--NQD RIEKLLTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_019314093
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_019315370
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_019803776
420
RAIIRRQAEFYPFLAD--NQD RIEKLLTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_019805234
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_024783594
420
RAIIRRQAEFYPFLAD--NQD RIEKLLTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_024784288
420
HAILRRQGDYYPFLKE--NQD RIEKILTFRIPYYVGPL ARKN--SRFAWAEY---HSDEAVTPWNFDQVIDKES
486


WP_024784666
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_024784894
420
RAIIRRQAEFYPFLAD--NQD RIEKLLTFRIPYYVGPL ASGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_024786433
420
HAILRRQGDYYPFLKE--NQD RIEKILTFRIPYYVGPL ARKN--SRFAWAEY---HSDEAVTPWNFDQVIDKES
486


WP_049473442
420
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


WP_049474547
420
RAIIRRQAEFYPFLAD--NQD RIEKLLTFRIPYYVGPL ASGK--SDFAWLSR---KSADKITPWNFDEIVDKES
486


EMC03581
413
RAIIRRQAEFYPFLAD--NQD RIEKILTFRIPYYVGPL ARGK--SDFAWLSR---KSADKITPWNFDEIVDKES
479


WP_000428612
421
NAILRRQGEHYPFLKE--NKE KIEKILTFRIPYYVGPL ARGN--RDFAWLTR---NSDQAIRPWNFEEIVDKAS
487


WP_000428613
421
NAILRRQGEHYPFLKD--NKE KIEKILTFRIPYYVGPL ARGN--RDFAWLTR---NSDEAIRPWNFEEIVDKAS
487


WP_049523028
420
NAILRHQGEYYPFLKE--NKD KIEQILTFRIPYYVGPL ARGN--SDFAWLSR---NSDEAIRPWNFEEMVDKSS
486


WP_003107102
389
KSIIRRQEKYYPFLKD--KQV RIEKIFTFRIPYFVGPL ANG-n-SSFAWVKR---RSNESITPWNFEEVVEQEA
455


WP_054279288
422
QAILERQQAYYPFLKD--NQE KIEKILTFRIPYYIGPL ARG-n-SRFAWLTR---TSDQKITPWNFDEMVDQEA
488


WP_049531101
421
NAILRRQGEHYPFLKE--NRE KIEKILTFRIPYYVGPL ARGN--RDFAWLTR---NSDQAIRPWNFEEIVDKAS
487


WP_049538452
421
NAILRRQGEHYPFLKE--NKE KIEKILTFRIPYYVGPL ARGN--RDFAWLTR---NSDQAIRPWNFEEIVDKAS
487


WP_049549711
421
NAILRRQGEHYPFLKE--NKE KIEKILTFRIPYYVGPL ARGN--RDFAWLTR---NSDQAIRPWNFEEIVDKAS
487


WP_007896501
422
HAILRRQEKYYPFLAE--QKE KIEQLLCFRIPYYVGPL AKGGn-SSFAWLKR---RSDEPITPWNFKDVVDEEA
489


EFR44625
374
HAILRRQEKYYPFLAE--QKE KIEQLLCFRIPYYVGPL AKGGn-SSFAWLKR---RSDEPITPWNFKDVVDEEA
441


WP_002897477
420
NAILRRQGEHYPFLKE--NRE KIEKILTFRIPYYVGPL ARDN--RDFSWLTR---NSDEPIRPWNFEEVVDKAR
486


WP_002906454
420
NAILRRQGEHYLFLKE--NRE KIEKILAFRIPYYVGPL ARGN--RDFAWLTR---NSDQAIRPWNFEEVVDKAS
486


WP_009729476
421
NAILRRQGEHYPFLKE--NKE KIEKILTFRIPYYVGPL ARGN--RDFAWLTR---NSDQAIRPWNFEEIVDKAS
487


CQR24647
421
KAILRRQGEFYPFLKE--NAE KIQQILTFKIPYYVGPL ARGN--SRFAWASY---NSNEKMTPWNFDNVIDKTS
487


WP_000066813
421
NAIIRRQGEHYPFLQE--NKE KIEKILTFRIPYYVGPL ARGN--GDFAWLTR---NSDQAIRPWNFEEIVDQAS
487


WP_009754323
421
NAILRRQGEHYPLLKE--NKE KIEKILTFRIPYYVGPL ARGN--RDFAWLTR---NSDQAIRPWNFEEIVDKAS
487


WP_044674937
420
HAIIRRQAEFYPFLVE--NQD KIEKILTFRIPYYVGPL ARGK--SEFAWLNR---KSDEKIRPWNFDEMVDKET
486


WP_044676715
420
HAIIRRQAEFYPFLVE--NQD KIEKILTFRIPYYVGPL ARGK--SEFAWLNR---KSDEKIRPWNFDEMVDKET
486


WP_044680361
420
HAIIRRQAEFYPFLVE--NQD KIEKILTFRIPYYVGPL ARGK--SEFAWLNR---KSDEKIRPWNFDEMVDKET
486


WP_044681799
420
HAIIRRQAEFYPFLVE--NQD KIEKILTFRIPYYVGPL ARGK--SEFAWLNR---KSDEKIRPWNFDEMVDKET
486


WP_049533112
420
HAILRRQEEHYPFLKE--NQD KIEKILTFRIPYYVGPL ARKG--SRFAWAEY---KADEKITPWNFDDILDKEK
486


WP_029090905
404
VAILENQATYYPELLE--QKD NIHKLLTFRIPYYVGPL ADQKd-SEFAWMVR---KQAGKITPFNFEEMVDIDA
471


WP_006506696
430
IKIIDNQAEYYPILKE--KRE QLLSILTFRIPYYFGPL ETSEh----AWIKRlegKENQRILPWNYQDIVDVDA
498


AIT42264
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_034440723
426
TAVLDQQEKHYSFLKE--NRD KIISLLTFRIPYYVGPL AKGE--SRFAWLER--sNSEEKIKPWNEDKIVDIDK
493


AKQ21048
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


WP_004636532
421
QAILDRQSQYYPFLAE--NRD KIESLVTFRIPYYVGPL TVSDq-SEFAWMER---QSDEPIRPWNFDEIVNKER
488


WP_002364836
428
QAIIHRQAAYYPFLKE--NQE KIEQLVTFRIPYYVGPL SKGDa-STFAWLKR---QSEEPIRPWNLQETVDLDQ
495


WP_016631044
379
QAIIHRQAAYYPFLKE--NQE KIEQLVTFRIPYYVGPL SKGDa-STFAWLKR---QSEEPIRPWNLQETVDLDQ
446


EMS75795
163
KAIIERQKPYYPSLEE--ARD KMIRLLTFRIPYYVGPL AQGEetSSFAWLER---KTPEKVTPWNATEVIDYSA
231


WP_002373311
428
QAIIHRQAAYYPFLKE--NQE KIEQLVTFRIPYYVGPL SKGDa-STFAWLKR---QSEEPIRPWNLQETVDLDQ
495


WP_002378009
428
QAIIHRQAAYYPFLKE--NQE KIEQLVTFRIPYYVGPL SKGDa-NTFAWLKR---QSEEPIRPWNLQETVDLDQ
495


WP_002407324
428
QAIIHRQAAYYPFLKE--NQE KIEQLVTFRIPYYVGPL SKGDa-STFAWLKR---QSEEPIRPWNLQETVDLDQ
495


WP_002413717
428
QAIIHRQAAYYPFLKE--NQE KIEQLVTFRIPYYVGPL SKGDa-STFAWLKR---QSEEPIRPWNLQETVDLDQ
495


WP_010775580
430
QAIIHRQAAYYPFLKE--NQK KIEQLVTFRIPYYVGPL SKGDa-STFAWLKR---QSEEPIRPWNLQETVDLDQ
497


WP_010818269
428
QAIIHRQAAYYPFLKE--NQE KIEQLVTFRIPYYVGPL SKGDa-STFAWLKR---QSEEPIRPWNLQETVDLDQ
495


WP_010824395
428
QAIIHRQAAYYPFLKE--NQE KIEQLVTFRIPYYVGPL SKGDa-STFAWLKR---QSEEPIRPWNLQETVDLDQ
495


WP_016622645
428
QAIIHRQAAYYPFLKE--NQE KIEQLVTFRIPYYVGPL SKGDa-STFAWLKR---QSEEPIRPWNLQETVDLDQ
495


WP_033624816
428
QAIIHRQAAYYPFLKE--NQK KIEQLVTFRIPYYVGPL SKGDa-STFAWLKR---QSEEPIRPWNLQETVDLDQ
495


WP_033625576
428
QAIIHRQAAYYPFLKE--NQE KIEQLVTFRIPYYVGPL SKGDa-STFAWLKR---QNEKPIRPWNLQETVDLDQ
495


WP_033789179
428
QAIIHRQAAYYPFLKE--NQK KIEQLVTFRIPYYVGPL SKGDa-STFAWLKR---QSEEPIRPWNLQETVDLDQ
495


WP_002310644
424
RAIIANQKKHYPFLKE--EQE KLESLLTFKIPYYVGPL AKKQenSPFAWLIR---KSEEKIKPWNLPEIVDMEG
492


WP_002312694
425
RAIIANQKKHYPFLKE--EQE KLESLLTFKIPYYVGPL AKKQenSPFAWLIR---KSEEKIKPWNLPEIVDMEG
493


WP_002314015
425
RAIIANQKKHYPFLKE--EQE KLESLLTFKIPYYVGPL AKKQenSPFAWLIR---KSEEKIKPWNLPEIVDMEG
493


WP_002320716
425
RAIIANQKKHYPFLKE--EQE KLESLLTFKIPYYVGPL AKKQenSPFAWLIR---KSEEKIKPWNLPEIVDMEG
493


WP_002330729
424
RAIIANQKKHYPFLKE--EQE KLESLLTFKIPYYVGPL AKKQenSPFAWLIR---KSEEKIKPWNLPEIVDMEG
492


WP_002335161
425
RAIIANQKKHYPFLKE--EQE KLESLLTFKIPYYVGPL AKKQenSPFAWLIR---KSEEKIKPWNLPEIVDMEG
493


WP_002345439
425
RAIIANQKKHYPFLKE--EQE KLESLLTFKIPYYVGPL AKKQenSPFAWLIR---KSEEKIKPWNLPEIVDMEG
493


WP_034867970
418
KAIIDQQKQHYPFLEE--AGP KIIALFKFRIPYYVGPL AKEQeaSSFAWIER---KTAEKINPWNFSEVVDIEK
486


WP_047937432
425
RAIIANQKKHYPFLKE--EQE KLESLLTFKIPYYVGPL AKKQenSPFAWLIR---KSEEKIKPWNLPEIVDMEG
493


WP_010720994
418
KAIIDQQKQHYPFLEE--AGP KIIALFKFRIPYYVGPL AKEQeaSSFAWIER---KTAEKINPWNFSEVVDIEK
486


WP_010737004
418
KAIIDQQKQHYPFLEE--AGP KIIALFKFRIPYYVGPL AKEQeaSSFAWIER---KTAEKINPWNFSEVVDIEK
486


WP_034700478
418
KAIIDQQKQHYPFLEE--AGP KIIALFKFRIPYYVGPL AKEQeaSSFAWIER---KTAEKINPWNFSEVVDIEK
486


WP_007209003
422
RAILRKQEKYYSFLKE--NHE KIEQIFKVRIPYYVGPL AKHNeqSRFAWNIR---KSDEPIRPWNMNDVVDENA
490


WP_023519017
418
REIMDRQKRFYPFLKG--AQG KIEKLLTFRIPYYVGPL AQEGq-SPFAWIKR---KSPSQITPWNFAEVVDKEN
485


WP_010770040
423
EAIIQKQATYYPFLAD--NKE EMKQLVTFRIPYYVGPL ADGN--SPFAWLER---ISSEPIRPGNLAEVVDIKK
489


WP_048604708
419
KAILHHQAMYYPFLQE--KFS NFVDLLTFRIPYYVGPL ANGN--SRFSWLSR---KSDEPIRPWNLAEVVDLSK
485


WP_010750235
418
KAIIDQQKQYYPFLEK--SKE KMIQLLTFRIPYYVGPL AQDKetSSFAWLER---KTTEKIKPWNAKDVIDYGA
486


AII16583
459
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
525


WP_029073316
436
NKILENQSVYYSDLKD--NED KIRSILTFRIPYYFGPL ITKDr--QFDWIIKkegKENERILPWNANEIVDVDK
506


WP_031589969
436
NKILENQSVYYSDLKD--NED KIRSILTFRIPYYFGPL ITKDr--QFDWIIKkegKENERILPWNANEIVDVDK
506


KDA45870
418
VAIVENQGKYYPFLRE--NKD KFEKILNFRIPYYVGPL ARGN--SKFAWLTR--a-GEGKITPYNFDEMIDKET
484


WP_039099354
426
DRIIENQQQYYPWLAE-1NPN KLDELVAFRVPYYVGPL QQQSsdAKFAWMIR---KAEGQITPWNFDDKVDRQA
509


AKP02966
416
EKIIDNQSQYYPFLKE--NKE KLLSILSFRIPYYVGPL -QSSekNPFAWMER---KSNGHARPWNFDEIVDREK
483


WP_010991369
426
EAILHQQAKYYPFLKE--NYD KIKSLVTFRIPYFVGPL ANGQ--SEFAWLTR---KADGEIRPWNIEEKVDFGK
492


WP_033838504
426
EAILHQQAKYYPFLKE--NYD KIKSLVTFRIPYFVGPL ANGQ--SEFAWLTR---KADGEIRPWNIEEKVDFGK
492


EHN60060
429
EAILHQQAKYYPFLKE--NYD KIKSLVTFRIPYFVGPL ANGQ--SEFAWLTR---KADGEIRPWNIEEKVDFGK
495


EFR89594
195
EAILHQQAKYYPFLKE--NYD KIKSLVTFRIPYFVGPL ANGQ--SEFAWLTR---KADGEIRPWNIEEKVDFGK
261


WP_038409211
426
EAILHQQAKYYPFLRK--DYE KIRSLVTFRIPYFIGPL ANGQ--SDFAWLTR---KADGEIRPWNIEEKVDFGK
492


EFR95520
45
EAILHQQAKYYPFLRK--DYE KIRSLVTFRIPYFIGPL ANGQ--SDFAWLTR---KADGEIRPWNIEEKVDFGK
111


WP_003723650
426
EAIIHQQAKYYPFLKE--DYD KIKSLVTFRIPYFVGPL ANGQ--SEFAWLTR---KADGEIRPWNIEEKVDFGK
492


WP_003727705
426
EAILHQQAKYYPFLRE--GYD KIKSLVTFRIPYFVGPL ANGQ--SEFAWLTR---KDDGEIRPWNIEEKVDFGK
492


WP_003730785
426
EAILHQQAKYYPFLRE--GYD KIKSLVTFRIPYFVGPL ANGQ--SEFAWLTR---KDDGEIRPWNIEEKVDFGK
492


WP_003733029
426
EAILHQQAKYYPFLRE--DYE KIKSLVTFRIPYFVGPL AKGQ--SEFAWLTR---KADGEIRPWNIEEKVDFGK
492


WP_003739838
426
EAILHQQAKYYPFLKE--AYD KIKSLVTFRIPYFVGPL ANGQ--SDFAWLTR---KADGEIRPWNIEEKVDFGK
492


WP_014601172
426
EAIIHQQAKYYPFLRE--DYE KIKSLVTFRIPYFVGPL AKGQ--SEFAWLTR---KADGEIRPWNIEEKVDFGK
492


WP_023548323
426
EAILHQQAKYYPFLRE--DYE KIKSLVTFRIPYFVGPL AKGQ--SEFAWLTR---KADGEIRPWNIEEKVDFGK
492


WP_031665337
426
EAIIHQQAKYYTFLKE--DYD KIKSLVTFRIPYFVGPL ANGQ--SEFAWLTR---KADGEIRPWNIEEKVDFGK
492


WP_031669209
426
EAILHQQAKYYPFLRE--DYE KIKSLVTFRIPYFVGPL AKGQ--SEFAWLTR---KADGEIRPWNIEEKVDFGK
492


WP_033920898
426
EAIIHQQAKYYPFLRE--DYE KIKSLVTFRIPYFVGPL AKGQ--SEFAWLTR---KADGEIRPWNIEEKVDFGK
492


AKI42028
429
EAIIHQQAKYYPFLRE--DYE KIKSLVTFRIPYFVGPL AKGQ--SEFAWLTR---KADGEIRPWNIEEKVDFGK
495


AKI50529
429
EAIIHQQAKYYPFLRE--DYE KIKSLVTFRIPYFVGPL AKGQ--SEFAWLTR---KADGEIRPWNIEEKVDFGK
495


EFR83390

--------------------- ----------------- ------------------------------------



WP_046323366
426
EAILHQQAKYYPFLKV--DYE KIKSLVTFRIPYFVGPL ANGQ--SEFSWLTR---KADGEIRPWNIEEKVDFGK
492


AKE81011
436
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
502


CUO82355
434
IKIIDNQAKYYPVLKE--KRE QLLSILTFRIPYYFGPL ETSEh----AWIKRlegKENQRILPWNYQDTVDVDA
502


WP_033162887
435
IQIIDNQSVYYPQLKE--NRD KLISILEFRIPYYFGPL AHSE----FAWIKKfedKQKERILPWNYDQIVDIDA
503


AGZ01981
453
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
519


AKA60242
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


AKS40380
420
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
486


4UN5_B
424
HAILRRQEDFYPFLKD--NRE KIEKILTFRIPYYVGPL ARG-n-SRFAWMTR---KSEETITPWNFEEVVDKGA
490


WP_010922251
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGcustom character QKKAIVDLLFK--TNR-KVTV
561


WP_039695303
490
SAEKFITRMTLNDLYLPEEKVLPKHSHVYETYAVYNELTKIKYVN--EQGKES-FFDSNMKQEIFDHVFK--ENR-KVTK
563


WP_045635197
487
SAEDFINKMTNYDLYLPEEKVLPKHSLLYETFAVYNELTKVKFIA--EGLRDYqFLDSGQKKQIVNQLFK--ENR-KVTE
561


5AXW_A
230
--KEWYEMLMGHCTYFFEELRSVKYAYNADLYNALNDLNNLVITR--DENEKLeYYE---KFQIIENVFK--QKK-KPTL
299


WP_009880683
171
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
245


WP_010922251
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_011054416
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_011284745
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_011285506
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_011527619
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_012560673
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_014407541
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_020905136
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_023080005
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_023610282
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_030125963
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_030126706
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_031488318
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPeFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_032460140
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_032461047
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_032462016
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_032462936
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_032464890
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_033888930
312
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
386


WP_038431314
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_038432938
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_038434062
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


BAQ51233
398
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
472


KGE60162

--------------------------------------------------------------------------------



KGE60856

--------------------------------------------------------------------------------



WP_002989955
487
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
561


WP_003030002
487
SAEKFITRMTLNDLYLPEEKVLPKHSLLYETFTVYNELTKVKYVN--EQGEAK-FFDANMKQEIFDHVFK--ENR-KVTK
560


WP_003065552
490
SAEKFITRMTLNDLYLPEEKVLPKHSHVYETYAVYNELTKIKYVN--EQGKDS-FFDSNMKQEIFDHVFK--ENR-KVTK
563


WP_001040076
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRFLA--EGFKDFqFLNRKQKETIFNSLFK--EKR-KVTE
562


WP_001040078
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_001040080
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_001040081
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_001040083
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_001040085
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_001040087
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_001040088
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_001040089
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_001040090
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_001040091
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_001040092
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNVKQEIFDGVFK--EHR-KVSK
561


WP_001040094
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRFLA--EGFKDFqFLNRKQKETIENSLEK--EKR-KVTE
562


WP_001040095
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRFLA--EGFKDFqFLNRKQKETIENSLEK--EKR-KVTE
562


WP_001040096
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRFLA--EGFKDFqFLNRKQKETIENSLEK--EKR-KVTE
562


WP_001040097
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRFLA--EGFKDFqFLNRKQKETIENSLEK--EKR-KVTE
562


WP_001040098
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRFLA--EGFKDFqFLNRKQKETIENSLEK--EKR-KVTE
562


WP_001040099
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRFLA--EGFKDFqFLNRKQKETIENSLEK--EKR-KVTE
562


WP_001040100
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRFLA--EGFKDFqFLNRKQKETIENSLEK--EKR-KVTE
562


WP_001040104
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_001040105
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_001040106
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_001040107
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_001040108
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_001040109
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_001040110
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_015058523
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNVKQEIFDGVFK--EHR-KVSK
561


WP_017643650
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRFLA--EGFKDFqFLNRKQKETIENSLEK--EKR-KVTE
562


WP_017647151
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_017648376
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_017649527
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_017771611
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


WP_017771984
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


CFQ25032
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


CFV16040
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIFDGVFK--EHR-KVSK
561


KLJ37842
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIEDGVEK--EHR-KVSK
561


KLJ72361
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIEDGVEK--EHR-KVSK
561


KLL20707
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIEDGVEK--EHR-KVSK
561


KLL42645
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIEDGVEK--EHR-KVSK
561


WP_047207273
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIEDGVEK--EHR-KVSK
561


WP_047209694
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRFLA--EGFKDFqFLNRKQKETIFNELFK--EKR-KVTE
562


WP_050198062
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIEDGVEK--EHR-KVSK
561


WP_050201642
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIEDGVEK--EHR-KVSK
561


WP_050204027
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIEDGVEK--EHR-KVSK
561


WP_050881965
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIEDGVEK--EHR-KVSK
561


WP_050886065
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIEDGVEK--EHR-KVSK
561


AHN30376
488
SAEAFIHRMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDENVKQEIEDGVEK--EHR-KVSK
561


EA078426
488
SAEAFIHRMTNNDFYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIEDGVEK--EHR-KVSK
561


CCW42055
488
SAEAFIHCMTNNDLYLPEEKVLPKHSLIYEKFTVYNELTKVRYKN--EQGETY-FFDSNIKQEIEDGVEK--EYR-KVSK
561


WP_003041502
487
SAEKFITRMTLNDLYLPEEKVLPKHELLYETFTVYNELTKVKYVN--EQGEAK-FFDANMKQEIFDHVFK--ENR-KVTK
560


WP_037593752
488
SAEKFITRMTLNDLYLPEEKVLPKHSPLYETFTVYNELTKVKYVN--EQGEAK-FFDTNMKQEIFDHVFK--ENR-KVTK
561


WP_049516684
488
SAEKFITRMTLNDLYLPEEKVLPKHSPLYETFTVYNELTKVKYVN--EQGEAK-FFDTNMKQEIFDHVFK--ENR-KVTK
561


GAD46167
487
SAEKFITRMTLNDLYLPEEKVLPKHSPLYETFTVYNELTKVKYVN--EQGEAK-FFDTNMKQEIFDHVFK--ENR-KVTK
560


WP_018363470
488
SAEKFITRMTLNDLYLPEEKVLPKHSHVYETFAVYNELTKVKYVN--EQGKDS-FFDSNMKQEIFDHVFK--ENR-KVTK
561


WP_003043819
497
SAQSFIERMTNEDEQLPNKKVLPKHELLYEYFTVYNELTKVKYVT--ERMRKPeFLSGEQKKAIVDLLFK--TNR-KVTV
571


WP_006269658
487
SAEKFITRMTLNDLYLPEEKVLPKHSPLYEAFTVYNELTKVKYVN--EQGEAK-FFDTNMKQEIFDHVFK--ENR-KVTK
560


WP_048800889
487
SAEKFITRMTLNDLYLPEEKVLPKHSLLYEIFTVYNELTKVKYVN--EQGEAK-FFDANMKQEIFDHVEK--ENP-KVTK
560


WP_012767106
487
SAQSFIERMTNEDKNLPNEKVLPKHELLYEYFTVYNELTKVKYVT--EGMRKPeFLEGKQKEAIVDLLFK--TNR-KVTV
561


WP_014612333
487
SAQSFIERMTNEDKNLPNEKVLPKHELLYEYFTVYNELTKVKYVT--EGMRKPeFLEGKQKEAIVDLLFK--TNR-KVTV
561


WP_015017095
487
SAQSFIERMTNEDKNLPNEKVLPKHELLYEYFTVYNELTKVKYVT--EGMRKPeFLEGKQKEAIVDLLFK--TNR-KVTV
561


WP_015057649
487
SAQSFIERMTNEDKNLPNEKVLPKHELLYEYFTVYNELTKVKYVT--EGMRKPeFLEGKQKEAIVDLLFK--TNR-KVTV
561


WP_048327215
487
SAQSFIERMTNEDKNLPNEKVLPKHELLYEYFTVYNELTKVKYVT--EGMRKPeFLEGKQKEAIVDLLFK--TNR-KVTV
561


WP_049519324
487
SAQSFIERMTNEDKNLPNEKVLPKHELLYEYFTVYNELTKVKYVT--EGMRKPaELSGEQKKAIVDLLFK--TNR-KVTV
561


WP_012515931
487
SAQIFIEKMTKNDLYLPNEKVLPKHELLYETFTVYNELTKVKYAT--EGMTRPqFLEADQKQAIVDLLFK--TNR-KVTV
561


WP_021320964
487
SAQIFIEKMTKNDLYLPNEKVLPKHELLYETFTVYNELTKVKYAT--EGMTRPqFLEADQKQAIVDLLFK--TNR-KVTV
561


WP_037581760
487
SAQIFIEKMTKNDLYLPNEKVLPKHELLYETFTVYNELTKVKYAT--EGMTRPqFLEADQKQAIVDLLFK--TNR-KVTV
561


WP_004232481
487
SAEKFITRMTLNDLYLPEEKVLPKHEYVYETFAVYNELTKIKYVN--EQGKSF-FFDANMKQEIFDHVFK--ENR-KVTK
560


WP_009854540
488
SAEKFITRMTLNDLYLPEEKVLPKHSHVYETYAVYNELTKIKYVN--EQGKES-FFDSNMKQEIFDHVFK--ENR-KVTK
561


WP_012962174
488
SAEKFITRMTLNDLYLPEEKVLPKHELVYETYTVYNELTKVKYVN--EQGKEN-FFDANMKQEIFEHVFK--ENR-KVTK
561


WP_039695303
490
SAEKFITRMTLNDLYLPEEKVLPKHSHVYETYAVYNELTKIKYVN--EQGKES-FFDSNMKQEIFDHVFK--ENR-KVTK
563


WP_014334983
487
SAEKFITRMTLNDLYLPEEKVLPKHSHVYETFTVYNELTKIKYVN--EQGESF-FFDANMKQEIFDHVFK--ENR-KVTK
560


WP_003099269
487
SARAFIERMTNFDTYLPEEKVLPKHSPLYEMFMVYNELTKVKYQT--EGMKRPvFLSSEDKEEIVNLLFK--KER-KVTV
561


AHY15608
487
SARAFIERMTNFDTYLPEEKVLPKHSPLYEMFMVYNELTKVKYQT--EGMKRPvFLSSEDKEEIVNLLFK--KER-KVTV
561


AHY17476
487
SARAFIERMTNFDTYLPEEKVLPKHSPLYEMFMVYNELTKVKYQT--EGMKRPvFLSSEDKEEIVNLLFK--KER-KVTV
561


ESR09100

--------------------------------------------------------------------------------



AGM98575
487
SARAFIERMTNFDTYLPEEKVLPKHSPLYEMFMVYNELTKVKYQT--EGMKRPvFLSSEDKEEIVNLLFK--KER-KVTV
561


ALF27331
487
SAEAFINRMTNYDLYLPNQKVLPRHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_018372492
500
SASRFIERMTLHDLYLPDEKVLPRHSLIYEKYTVFNELTKVRFTP--EGGKEV-YFSKTDKENIFDSLFK--RYR-KVTK
573


WP_045618028
488
SAEDFINKMTNYDLYLPEEKVLPKHSLLYETFAVYNELTKVKFIA--EGLRDYqFLDSGQKQQIVTQLFK--EKR-KVTE
562


WP_045635197
487
SAEDFINKMTNYDLYLPEEKVLPKHSLLYETFAVYNELTKVKFIA--EGLRDYqFLDSGQKKQIVNQLFK--ENR-KVTE
561


WP_002263549
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002263887
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELIKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002264920
487
SVEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002269043
487
SVEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002269448
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002271977
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002272766
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002273241
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002275430
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002276448
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002277050
487
SAQAFIEHMTNNDLYLPNEKVLPKHSPLYEKYTVYNELTKIKYVT--EIGEAK-FFDANLKQEIFDGLFK--HER-KVTK
560


WP_002277364
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002279025
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGETA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002279859
487
SVEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002280230
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002281696
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002282247
487
SAQAFIEHMTNNDLYLPNEKVLPKHSPLYEKYTVYNELTKIKYVT--EIGEAK-FFDANLKQEIFDGLFK--HER-KVTK
560


WP_002282906
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002283846
487
SVEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002287255
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002288990
487
SVEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002289641
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002290427
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002295753
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002296423
487
SVEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002304487
497
SAEKFITRMTLNDLYLPEEKVLPKHSLLYETFTVYNELTKVKYVN--EQGEAK-FFDANMKQEIFDHVFK--ENR-KVTK
570


WP_002305844
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002307203
487
SVEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002310390
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_002352408
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_012997688
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_014677909
487
SVEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_019312892
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_019313659
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_019314093
487
SVEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_019315370
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_019803776
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_019805234
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_024783594
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_024784288
487
SAQAFIEHMTNNDLYLPNEKVLPKHSPLYEKYTVYNELTKIKYVT--EIGEAK-FFDANLKQEIFDGLFK--HER-KVTK
560


WP_024784666
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_024784894
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_024786433
487
SAQAFIEHMTNNDLYLPNEKVLPKHSPLYEKYTVYNELTKIKYVT--EIGEAK-FFDANLKQEIFDGLFK--HER-KVTK
560


WP_049473442
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


WP_049474547
487
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
560


EMC03581
480
SAEAFINRMTNYDLYLPNQKVLPKHSLLYEKFTVYNELTKVKYKT--EQGKTA-FFDANMKQEIFDGVFK--VYR-KVTK
553


WP_000428612
488
SAESFINKMTNYDLYLPEEKVLPKHSLLYETFAVYNELTKVKFIA--EGLRDYqFLDSRQKKDIFYTLFKaeDKR-KVTE
564


WP_000428613
488
SAEDFINKMTNYDLYLPEEKVLPKHSLLYETFAVYNELTKVKFIA--EGLRDYqFLDSGQKKQIVTQLFK--EKR-KVTE
562


WP_049523028
487
SAEDFIHRMTNYDLYLPEEKVLPKHSLLYETFTVYNELTKVKYIA--EGMKDYqFLDSGQKKQIVNQLFK--EKR-KVTE
561


WP_003107102
456
SAKVFIERMTNFDTYLPEEKVLPKHSLLYEMFTVYNELTKVKYQA--EGMRKPeFLSSEEKIEIVSNLFK--TER-KVTV
530


WP_054279288
489
SAQAFIERMTNFDEYLPQEKVLPKHSLTYEYFTVYNELTKVKYVT--EGMTKPeFLSAGQKEQIVELLFK--KYR-KVTV
563


WP_049531101
488
SAEAFINKMTNYDLYLPEEKVLPKHSLLYETFAVYNELTKVKFIA--EGLRDYqFLDSGQKKKIINQLFK--EKR-KVTE
562


WP_049538452
488
SAEDFINKMTNYDLYLPEEKVLPKHSLLYETFAVYNELTKVKFIA--EGLRDYqFLDSGQKKQIVNQLFK--EKR-KVTE
562


WP_049549711
488
SAEDFINKMTNYDLYLPEEKVLPKHSLLYETFAVYNELTKVKFIA--EGLRDYqFLDSGQKKQIVNQLFK--EKR-KVTE
562


WP_007896501
490
SAQAFIEGMTNYDTYLPEEKVLPKHSPLYEMFTVYNELTKVKYIA--ENMTKPlYLSAEQKEATIDHLFK--QTR-KVTV
564


EFR44625
442
SAQAFIEGMTNYDTYLPEEKVLPKHSPLYEMFTVYNELTKVKYIA--ENMTKPlYLSAEQKEATIDHLFK--QTR-KVTV
516


WP_002897477
487
SAEDFIHRMTNYDLYLPEEKVLPKHSLLYETFAVYNELTKVKFIA--EGLRDYqFLDSGQKKQIVNQLFK--EKR-KVTE
561


WP_002906454
487
SAEDFINKMTNYDLYLPEEKVLPKHSLLYETFAVYNELTKVKFIA--EGLRDYqFLDSGQKKQIVNQLFK--DKR-KVTE
561


WP_009729476
488
SAEDFINKMTNYDLYLPEEKVLPKHSLLYETFAVYNELTKVKFIA--EGLRDYqFLDSGQKKQIVTQLFK--EKR-KVTE
562


CQR24647
488
SAQAFIERMTNNDLYLPDQKVLPKHSLLYQKFAVYNELTKIKYVT--ETGEAR-LEDVFLKKEIFDGLEK--KER-KVTK
561


WP_000066813
488
SAEDFINKMTNYDLYLPEEKVLPKHSLLYETFAVYNELTKVKFIA--EGLTRYqFLDKKQKKDIFDTFFKaeNKR-KVTE
564


WP_009754323
488
SAESFINKMTNYDLYLPEEKVLPKHSLLYETFAVYNELTKVKFIA--EGLRDYqFFDSGQKKQIVNQLFK--EKR-KVTE
562


WP_044674937
487
SAENFITRMTNYDQYLPDQKVLPKHSLLYEKFAVYNELTKVKFIA--EGMRDYqFLDSGQKKDIVKTLFK--TKR-KVTA
561


WP_044676715
487
SAENFITRMTNYDQYLPDQKVLPKHSLLYEKFAVYNELTKVRYVT--EQGKSF-FFDANMKQEIFDGVEK--VYR-KVTK
560


WP_044680361
487
SAENFITRMTNYDQYLPDQKVLPKHSLLYEKFAVYNELTKVRYVT--EQGKSF-FFDANMKQEIFDGVEK--VYR-KVTK
560


WP_044681799
487
SAENFITRMTNYDQYLPDQKVLPKHSLLYEKFAVYNELTKVKFIA--EGMRDYqFLDSGQKKDIVKTLFK--TKR-KVTA
561


WP_049533112
487
SAEKFITRMTLNDLYLPEEKVLPKHSLLYETFTVYNELTKVKYVN--EQGEAK-FFDANMKQEIFDHVEK--ENR-KVTK
560


WP_029090905
472
SSEAFIKRMTNKCTYLIHEDVIPKHSFSYAKFEVLNELNKIRLDG------KP--IDIPLKKRIFEGLFL---EKtKVTQ
540


WP_006506696
499
TAEGFIKRMRSYCTYFPDEEVLPKNSLIVSKYEVYNELNKIRVDD--------kLLEVDVKNDIYNELFM--KNK-TVTE
567


AIT42264
487
SAQSFIERMTNEDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaELSGEQKKAIVDLLFK--TNR-KVTV
561


WP_034440723
494
SAELFIENLTSRDTYLPDEPVLPKRSLIYQKFTIFNELTKISYID--ERGILQ-NFSSREKIAIENDLFK---NKsKVTK
567


AKQ21048
487
SAQSFIERMTNEDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaELSGEQKKAIVDLLFK--TNR-KVTV
561


WP_004636532
489
SAEKFIERMTNMDTYLLEEKVLPKRSLLYQTFEVYNELTKVRYTN--EQGKTE-KLNRQQKAEIIETLFK-qKNR--VRE
562


WP_002364836
496
SATAFIERMTNEDTYLPSEKVLPKHSLLYEKFMVFNELTKISYTD--DRGIKA-NFSGKEKEKIFDYLFK--TRR-KVKK
569


WP_016631044
447
SATAFIERMTNEDTYLPSEKVLPKHSLLYEKFMVFNELTKISYTD--DRGIKA-NFSGKEKEKIFDYLFK--TRR-KVKK
520


EMS75795
232
SAMKFIQRMINYDTYLPTEKVLPKHSILYQKYTIFNELTKVAYKD--ERGIKH-QESSKEKREIFKELFQ--KQR-KVTV
305


WP_002373311
496
SATAFIERMTNEDTYLPSEKVLPKHSLLYEKFMVFNELTKISYTD--DRGIKA-NFSGKEKEKIFDYLFK--TRR-KVKK
569


WP_002378009
496
SATAFIERMTNEDTYLPSEKVLPKHSLLYEKFMVFNELTKISYTD--DRGIKA-NFSGKEKEKIFDYLFK--TRR-KVKK
569


WP_002407324
496
SATAFIERMTNEDTYLPSEKVLPKHSLLYEKFMVFNELTKISYTD--DRGIKA-NFSGKEKEKIFDYLFK--TRR-KVKK
569


WP_002413717
496
SATAFIERMTNEDTYLPSEKVLPKHSLLYEKFMVFNELTKISYTD--DRGIKA-NFSGKEKEKIFDYLFK--TRR-KVKK
569


WP_010775580
498
SATAFIERMTNEDTYLPSEKVLPKHSLLYEKFMVFNELTKISYTD--DRGIKA-NFSGKEKEKIFDYLFK--TRR-KVKK
571


WP_010818269
496
SATAFIERMTNEDTYLPSEKVLPKHSLLYEKFMVFNELTKISYTD--DRGIKA-NFSGKEKEKIFDYLFK--TRR-KVKK
569


WP_010824395
496
SATAFIERMTNEDTYLPSEKVLPKHSLLYEKFMVFNELTKISYTD--DRGIKA-NFSGKEKEKIFDYLFK--TRR-KVKK
569


WP_016622645
496
SATAFIERMTNEDTYLPSEKVLPKHSLLYEKFMVFNELTKISYTD--DRGIKA-NFSGKEKEKIFDYLFK--TRR-KVKK
569


WP_033624816
496
SATAFIERMTNEDTYLPSEKVLPKHSLLYEKFMVFNELTKISYTD--DRGIKA-NFSGKEKEKIFDYLFK--TRR-KVKK
569


WP_033625576
496
SATAFIERMTNEDTYLPSEKVLPKHSLLYEKFMVFNELTKISYTD--DRGIKA-NFSGKEKEKIFDYLFK--TRR-KVKK
569


WP_033789179
496
SATAFIERMTNEDTYLPSEKVLPKHSLLYEKFMVFNELTKISYTD--DRGIKA-NFSGKEKEKIFDYLFK--TRR-KVKK
569


WP_002310644
493
SAVRFIERMINTDMYMPHNKVLPKNSLLYQKFSIYNELTKVRYQD--ERGQMN-YFSSIEKKEIFHELFE--KNR-KVTK
566


WP_002312694
494
SAVRFIERMINTDMYMPHNKVLPKNSLLYQKFSIYNELTKVRYQD--ERGQMN-YFSSIEKKEIFHELFE--KNR-KVTK
567


WP_002314015
494
SAVRFIERMNNTDMYIPHNKVLPKNSLLYQKFSIYNELTKVRYQD--ERGQMN-YFSSIEKKEIFHELFE--KNR-KVTK
567


WP_002320716
494
SAVRFIERMINTDMYIPHNKVLPKNSLLYQKFSIYNELTKVRYQD--ERGQMN-YFSSIEKKEIFHELFE--KNR-KVTK
567


WP_002330729
493
SAVRFIERMINTDMYIPHNKVLPKNSLLYQKFSIYNELTKVRYQD--ERGQMN-YESSIEKKEIFHELFE--KNR-KVTK
566


WP_002335161
494
SAVRFIERMINTDMYMPHNKVLPKNSLLYQKFSIYNELTKVRYQD--ERGQMN-YESSIEKKEIFHELFE--KNR-KVTK
567


WP_002345439
494
SAVRFIERMINTDMYIPHNKVLPKNSLLYQKFSIYNELTKVRYQD--ERGQMN-YESSIEKKEIFHELFE--KNR-KVTK
567


WP_034867970
487
SAMRFIQRMTKQDTYLPTEKVLPKNSLLYQKYMIFNELTKVSYKD--ERGVKQ-YFSGDEKQQIFKQLFQ--KERgKITV
561


WP_047937432
494
SAVRFIERMINTDMYMPHNKVLPKNSLLYQKFSIYNELTKVRYQD--ERGQMN-YESSIEKKEIFHELFE--KNR-KVTK
567


WP_010720994
487
SAMRFIQRMTKQDTYLPTEKVLPKNSLFYQKYMIFNELTKVSYKD--ERGVKQ-YFSGDEKQQIFKQLFQ--KERgKITV
561


WP_010737004
487
SAMRFIQRMTKQDTYLPTEKVLPKNSLLYQKYMIFNELTKVSYKD--ERGVKQ-YFSGDEKQQIFKQLFQ--KERgKITV
561


WP_034700478
487
SAMRFIQRMTKQDTYLPTEKVLPKNSLLYQKYMIFNELTKVSYKD--ERGVKQ-YFSGDEKQQIFKQLFQ--KERgKITV
561


WP_007209003
491
SAVAFIERMTIKDIYL-NENVLPRHSLIYEKFTVFNELTKVLYAD--DRGVFQ-RFSAEEKEDIFEKLFK--SER-KVTK
563


WP_023519017
486
SAIEFIERMTNQDTYLPKEKVLPKQSLIYQRFMIFNELTKVSYTD--ERGKSH-YFSSEQKRKIFNELFK--QHP-RVTE
559


WP_010770040
490
SATKFIERMTNEDTYLPTEKVLPKHSMIYEKYMVYNELTKVSYVD--ERGMNQ-RFSGEEKKQIVEELFK--QSR-KVTK
563


WP_048604708
486
SAELFIERMTNFDLYLPSEKVLPKHSMLYEKYTVYNELTKVTYKD--EQGKVQ-NFSSEEKERIFIDLFK--QHR-KVTK
559


WP_010750235
487
SATKFIQRMINYDTYLPTEKVLPKYSMLYQKYTIFNELTKVAYKD--DRGIKH-QFSSEEKLRIFQELFK--KQR-RVTK
560


AII16583
526
SAQSFIERMTNFDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaFLSGEQKKAIVDLLFK--TNR-KVTV
600


WP_029073316
507
TADEFIKRMRNFCTYFPDEPVLAKNSLTVSKYEVLNEINKLRIND--------hLIKRDIKDKMLHTLFM--DHK-SISA
575


WP_031589969
507
TADEFIKRMRNFCTYFPDEPVMAKNSLTVSKYEVLNEINKLRIND--------hLIKRDMKDKMLHTLFM--DHK-SISA
575


KDA45870
485
SAEDFIKRMTINDLYLPTEPVLPKHSLLYERYTIFNELAGVRYVT--ENGEAK-YEDAQTKRSIFE-LFK1--DR-KVSE
557


WP_039099354
510
SANEFIKRMTTTDTYLLAEDVLPKQSLIYQRFEVLNELNGLKIDD--QPITTE------LKQAIFTDLFM---QKtSVTV
578


AKP02966
484
SSNKFIRRMTVTDSYLVGEPVLPKNSLIYQRYEVLNELNNIRITEn1KTNPTGsRLTVETKQHIYNELFK--NYK-KITV
560


WP_010991369
493
SAVDFIEKMTNKDTYLPKENVLPKHSLCYQKYLVYNELTKVRYIN--DQGKTS-YFSGQEKEQIENDLFK--QKR-KVKK
566


WP_033838504
493
SAVDFIEKMTNKDTYLPKENVLPKHSLCYQKYLVYNELTKVRYIN--DQGKTS-YFSGQEKEQIENDLFK--QKR-KVKK
566


EHN60060
496
SAVDFIEKMTNKDTYLPKENVLPKHSLCYQKYLVYNELTKVRYIN--DQGKTS-YFSGQEKEQIENDLFK--QKR-KVKK
569


EFR89594
262
SAVDFIEKMTNKDTYLPKENVLPKHSLCYQKYLVYNELTKVRYIN--DQGKTS-YFSGQEKEQIENDLFK--QKR-KVKK
335


WP_038409211
493
SAIDFIEKMTNKDTYLPKENVLPKHSLCYQKYMVYNELTKIRYID--DQGKTH-HFSGQEKQQIFNGLFK--QQR-KVKK
566


EFR95520
112
SAIDFIEKMTNKDTYLPKENVLPKHSLCYQKYMVYNELTKIRYID--DQGKTH-HFSGQEKQQIFNGLFK--QQR-KVKK
185


WP_003723650
493
SAVDFIEKMTNKDTYLPKENVLPKHSLCYQKYMVYNELTKIRYID--DQGKTN-YFSGREKQQVFNDLFK--QKR-KVKK
566


WP_003727705
493
SAVDFIEKMTNKDTYLPKENVLPKHSLCYQKYMVYNELTKIRYID--DQGKTN-YFSGREKQQIENDLFK--QKR-KVKK
566


WP_003730785
493
SAVDFIEKMTNKDTYLPKENVLPKHSLCYQKYMVYNELTKIRYID--DQGKTN-YFSGREKQQIENDLFK--QKR-KVKK
566


WP_003733029
493
SAVDFIEKMTNKDTYLPKENVLPKHSLCYQKYMVYNELTKVRYID--DQGKTN-YFSGQEKQQIENDLFK--QKR-KVKK
566


WP_003739838
493
SAVDFIEKMTNKDTYLPKENVLPKHSLYYQKYMVYNELTKVRYID--DQGKTN-YFSGQEKQQIENDYFK--QKR-KVSK
566


WP_014601172
493
SAVDFIEKMTNKDTYLPKENVLPKHSLCYQKYMVYNELTKVRYID--DQGKTN-YFSGQEKQQIENDLFK--QKR-KVKK
566


WP_023548323
493
SAVDFIEKMTNKDTYLPKENVLPKHSLCYQKYMVYNELTKIRYID--DQGKTN-YFSGQEKQQIENDLFK--QKR-KVKK
566


WP_031665337
493
SAVDFIEKMTNKDTYLPKENVLPKHSLCYQKYMVYNELTKVRYID--DQGKTN-YFSGQEKQQIENDLFK--QKR-KVKK
566


WP_031669209
493
SAVDFIEKMTNKDTYLPKENVLPKHSLCYQKYMVYNELTKVRYID--DQGKTN-YFSGQEKQQIENDLFK--QKR-KVKK
566


WP_033920898
493
SAVDFIEKMTNKDTYLPKENVLPKHSLCYQKYMVYNELTKIRYID--DQGKTN-YESGQEKQQIENDLEK--QKR-KVKK
566


AKI42028
496
SAVDFIEKMTNKDTYLPKENVLPKHSLCYQKYMVYNELTKVRYID--DQGKTN-YESGQEKQQIENDLEK--QKR-KVKK
569


AKI50529
496
SAVDFIEKMTNKDTYLPKENVLPKHSLCYQKYMVYNELTKIRYID--DQGKTN-YESGQEKQQIENDLEK--QKR-KVKK
569


EFR83390
1
---------------------------------------------------------------IFNDLEK--QKR-KVKK
14


WP_046323366
493
SAIDFIEKMTNKDTYLPKENVLPKHSMCYQKYMVYNELTKIRYTD--DQGKTH-YESGQEKQQIENDLEK--QKR-KVKK
566


AKE81011
503
SAQSFIERMTNEDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaELSGEQKKAIVDLLFK--TNR-KVTV
577


CUO82355
503
TAEGFIKRMRSYCTYFPDEEVLPKNSLIVSKYEVYNELNKIRVDD--------kLLEVDVKNDIYNELFM--KNK-TVTE
571


WP_033162887
504
TAEGFIERMKNTGTYFPDEPVMAKNSLTVSKFEVLNELNKIRING--------kLIAVETKKELLSDLFM--KNK-TITD
572


AGZ01981
520
SAQSFIERMTNEDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaELSGEQKKAIVDLLFK--TNR-KVTV
594


AKA60242
487
SAQSFIERMTNEDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaELSGEQKKAIVDLLFK--TNR-KVTV
561


AKS40380
487
SAQSFIERMTNEDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaELSGEQKKAIVDLLFK--TNR-KVTV
561


4UN5_B
491
SAQSFIERMTNEDKNLPNEKVLPKHSLLYEYFTVYNELTKVKYVT--EGMRKPaELSGEQKKAIVDLLFK--TNR-KVTV
565


WP_010922251
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_039695303
564
EKLLNYLNKE--FPEYRIKDLIGLDKEnkSFNASLGTYHDLKKIL-DK AFLDDKVNEEVIEDIIKTLTLFEDKDMIH
637


WP_045635197
562
KDIIHYLHN---VDGYDGIELKGIEKQ---FNASLSTYHDLLKIIKDK EFMDDAKNEAILENIVHTLTIFEDREMIK
632


5AXW_A
300
KQIAKEILVNe--EDIKGYRVTSTGKPe---FTNLKVYHDIKDITARK ------ENAELLDQIAKILTIYQSSEDIQ
368


WP_009880683
246
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
317


WP_010922251
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_011054416
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_011284745
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_011285506
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_011527619
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_012560673
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_014407541
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGAYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDRGMIE
633


WP_020905136
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_023080005
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNTSLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDKEMIE
633


WP_023610282
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNTSLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDKEMIE
633


WP_030125963
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_030126706
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_031488318
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_032460140
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_032461047
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_032462016
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_032462936
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDKEMIE
633


WP_032464890
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_033888930
387
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
458


WP_038431314
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_038432938
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNTSLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDKEMIE
633


WP_038434062
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


BAQ51233
473
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
544


KGE60162

------------------------------------------------ -----------------------------



KGE60856

------------------------------------------------ -----------------------------



WP_002989955
562
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_003030002
561
DKLLNYLNKE--FEEFRIVNLTGLDKEnkAFNSSLGTYHDLRKIL-DK SFLDDKANEKTIEDIIQTLTLFEDREMIR
634


WP_003065552
564
EKLLNYLNKE--FPEYRIKDLIGLDKEnkSFNASLGTYHDLKKIL-DK AFLDDKVNEEVIEDIIKTLTLFEDKDMIH
637


WP_001040076
563
KDIISFLNK---VDGYEGIAIKGIEKQ---FNASLSTYHDLKKIL-GK DFLDNTDNELILEDIVQTLTLFEDREMIK
632


WP_001040078
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_001040080
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_001040081
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_001040083
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIIQTLTLFEDREMIK
635


WP_001040085
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_001040087
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_001040088
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_001040089
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_001040090
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_001040091
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_001040092
562
KQLLDFLAKE--FEEFRIVDVTGLDKEnkAFNASLGTYHDLKKIL-DK DFLDNPDNESILEDIVQTITLFEDREMIK
635


WP_001040094
563
KDIISFLNK---VDGYEGIAIKGIEKQ---FNASLSTYHDLKKIL-GK DFLDNTDNELILEDIVQTLTLFEDREMIR
632


WP_001040095
563
KDIISFLNK---VDGYEGIAIKGIEKQ---FNASLSTYHDLKKIL-GK DFLDNTDNELILEDIVQTLTLFEDREMIR
632


WP_001040096
563
KDIISFLNK---VDGYEGIAIKGIEKQ---FNASLSTYHDLKKIL-GK DFLDNTDNELILEDIVQTLTLFEDREMIR
632


WP_001040097
563
KDIISFLNK---VDGYEGIAIKGIEKQ---FNASLSTYHDLKKIL-GK DFLDNTDNELILEDIVQTLTLFEDREMIR
632


WP_001040098
563
KDIISFLNK---VDGYEGIAIKGIEKQ---FNASLSTYHDLKKIL-GK DFLDNTDNELILEDIVQTLTLFEDREMIR
632


WP_001040099
563
KDIISFLNK---VDGYEGIAIKGIEKQ---FNASLSTYHDLKKIL-GK DFLDNTDNELILEDIVQTLTLFEDREMIR
632


WP_001040100
563
KDIISFLNK---VDGYEGIAIKGIEKQ---FNASLSTYHDLKKIL-GK DFLDNTDNELILEDIVQTLTLFEDREMIR
632


WP_001040104
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_001040105
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_001040106
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLKKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_001040107
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLKKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_001040108
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLKKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_001040109
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLKKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_001040110
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLKKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_015058523
562
KQLLDFLAKE--FEEFRIVDVTGLDKEnkAFNASLGTYHDLKKIL-DK DFLDNPDNESILEDIVQTITLFEDREMIK
635


WP_017643650
563
KDIISFLNK---VDGYEGIAIKGIEKQ---FNASLSTYHDLKKIL-GK DFLDNTDNELILEDIVQTLTLFEDREMIR
632


WP_017647151
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLKKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_017648376
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLKKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_017649527
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_017771611
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLKKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_017771984
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


CFQ25032
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


CFV16040
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


KLJ37842
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


KLJ72361
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


KLL20707
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


KLL42645
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLKKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_047207273
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_047209694
563
KDIISELNK---VDGYEGIAIKGIEKQ---FNASLSTYHDLKKIL-GK DFLDNTDNELILEDIVQTLTLFEDREMIR
632


WP_050198062
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_050201642
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_050204027
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLKKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_050881965
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_050886065
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


AHN30376
562
KQLLDFLAKE--FEEFRIVDVTGLDKEnkAFNASLGTYHDLKKIL-DK DFLDNPDNESILEDIVQTITLFEDREMIK
635


EA078426
562
KKLLDFLAKE--YEEFRIVDVIGLDKEnkAFNASLGTYHDLEKIL-DK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


CCW42055
562
KQLLDFLAKE--FEEFRIVDVTGLDKEnkAFNASLGTYHDLEKIL-GK DFLDNPDNESILEDIVQTLTLFEDREMIK
635


WP_003041502
561
DKLLNYLNKE--FEEFRIVNLTGLDKEnkVENSSLGTYHDLRKIL-NK SFLDNKENAQIIEDIIQTLTLFEDREMIR
634


WP_037593752
562
DKLLNYLNKE--FEEFRIVNLTGLDKEnkAENSSLGTYHDLRKIL-DK SFLDDKANEKTIEDIIQTLTLFEDREMIR
635


WP_049516684
562
DKLLNYLNKE--FEEFRIVNLTGLDKEnkAFNASLGTYHDLRKIL-DK SFLDDKVNEKIIEDIIQTLTLFEDREMIR
635


GAD46167
561
DKLLNYLNKE--FEEFRIVNLTGLDKEnkAENSSLGTYHDLRKIL-DK SFLDDKANEKTIEDIIQTLTLFEDREMIR
634


WP_018363470
562
EKLLNYLDKE--FPEYRIQDLVGLDKEnkSFNASLGTYHDLKKIL-DK SFLDDKVNEEVIEDIIKTLTLFEDREMIQ
635


WP_003043819
572
KQLKEDYFKK--IECEDSVEIIGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
643


WP_006269658
561
DKLLNYLNKE--FEEFRIVNLTGLDKEnkAENSSLGTYHDLRKIL-DK SFLDDKANEKTIEDIIQTLTLFEDREMIR
634


WP_048800889
561
DKLLNYLDKE--FDEFRIVDLTGLDKEnkAFNASLGTYHDLRKIL-DK SFLDDKANEKTIEDIIQTLTLFEDREMIR
634


WP_012767106
562
KQLKEDYFKK--IECEDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDKEMIE
633


WP_014612333
562
KQLKEDYFKK--IECEDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDKEMIE
633


WP_015017095
562
KQLKEDYFKK--IECEDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDKEMIE
633


WP_015057649
562
KQLKEDYFKK--IECEDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDKEMIE
633


WP_048327215
562
KQLKEDYFKK--IECEDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDKEMIE
633


WP_049519324
562
KQLKEDYFKK--IECEDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDKEMIE
633


WP_012515931
562
KQLKENYFKK--IECWDSVEITGVEDS---FNASLGTYHDLLKIIQDK DFLDNPDNQKIIEDIILTLTLFEDKKMIS
633


WP_021320964
562
KQLKENYFKK--IECWDSVEITGVEDS---FNASLGTYHDLLKIIQDK DFLDNPDNQKIIEDIILTLTLFEDKKMIS
633


WP_037581760
562
KQLKENYFKK--IECWDSVEITGVEDS---FNASLGTYHDLLKIIQDK DFLDNPDNQKIIEDIILTLTLFEDKKMIS
633


WP_004232481
561
AKLLSYLNNE--FEEFRINDLIGLDKDskSFNASLGTYHDLKKIL-DK SFLDDKTNEQIIEDIVLTLTLFEDRDMIH
634


WP_009854540
562
EKLLNYLNKE--FPEYRIKDLIGLDKEnkSFNASLGTYHDLKKIL-DK AFLDDKVNEEVIEDIIKTLTLFEDKDMIH
635


WP_012962174
562
DKFLNYLNKE--FPEYRIQDLIGLDKEnkSFNASLGTYHDLKKIL-DK SFLDDKTNETIIEDIIQTLTLFEDRDMIR
635


WP_039695303
564
EKLLNYLNKE--FPEYRIKDLIGLDKEnkSFNASLGTYHDLKKIL-DK AFLDDKVNEEVIEDIIKTLTLFEDKDMIH
637


WP_014334983
561
AKLLSYLNNE--FEEFRINDLIGLDKDskSFNASLGTYHDLKKIL-DK SFLDDKTNGQIIEDIVLTLTLFEDRDMIH
634


WP_003099269
562
KQLKEEYESK--MKCFHTVTILGVEDR---FNASLGTYHDLLKIFKDK AFLDDEANQDILEEIVWTLTLFEDQAMIE
633


AHY15608
562
KQLKEEYESK--MKCFHTVTILGVEDR---FNASLGTYHDLLKIFKDK AFLDDEANQDILEEIVWTLTLFEDQAMIE
633


AHY17476
562
KQLKEEYESK--MKCFHTVTILGVEDR---FNASLGTYHDLLKIFKDK AFLDDEANQDILEEIVWTLTLFEDQAMIE
633


ESR09100

------------------------------------------------ -----------------------------



AGM98575
562
KQLKEEYESK--MKCFHTVTILGVEDR---FNASLGTYHDLLKIFKDK AFLDDEANQDILEEIVWTLTLFEDQAMIE
633


ALF27331
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_018372492
574
RKLKDFIEKElgYGYIDIDNIKGVEEQ---FNASYTTYQDLLKIIGDK EFLDNEENKDLLEEIIYILTVFEDRKMIE
647


WP_045618028
563
KDIIQYLHN---VDSYDGIELKGIEKQ---FNASLSTYHDLLKIIKDK EFMDDSKNEAILENIVHTLTIFEDREMIK
633


WP_045635197
562
KDIIHYLHN---VDGYDGIELKGIEKQ---FNASLSTYHDLLKIIKDK EFMDDAKNEAILENIVHTLTIFEDREMIK
632


WP_002263549
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkVFNASYGTYHDLCKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002263887
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkVFNASYGTYHDLCKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002264920
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002269043
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002269448
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkVFNASYGTYHDLCKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002271977
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkVFNASYGTYHDLCKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002272766
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkVFNASYGTYHDLCKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002273241
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkVFNASYGTYHDLCKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002275430
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002276448
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkVFNASYGTYHDLCKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002277050
561
KKLRTFLDKN--FDEFRIVDIQGLDKEteTENASYATYQDLLKVIKDK VFMDNPENAEILENIVLTLTLFEDREMIK
635


WP_002277364
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002279025
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002279859
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002280230
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkVFNASYGTYHDLCKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002281696
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002282247
561
KKLRTFLDKN--FDEFRIVDIQGLDKEteTENASYATYQDLLKVIKDK VFMDNPENAEILENIVLTLTLFEDREMIK
635


WP_002282906
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkVFNASYGTYHDLCKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002283846
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002287255
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002288990
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002289641
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkVFNASYGTYHDLCKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002290427
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002295753
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkVFNASYGTYHDLCKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002296423
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002304487
571
DKLLNYLNKE--FEEFRIVNLTGLDKEnkVENSSLGTYHDLRKIL-NK SFLDNKENEQIIEDIIQTLTLFEDREMIR
644


WP_002305844
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkVFNASYGTYHDLCKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002307203
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002310390
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_002352408
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_012997688
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_014677909
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_019312892
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_019313659
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkVFNASYGTYHDLCKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_019314093
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_019315370
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_019803776
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkVFNASYGTYHDLCKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_019805234
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_024783594
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkVFNASYGTYHDLCKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_024784288
561
KKLRTFLDKN--FDEFRIVDIQGLDKEteTFNASYATYQDLLKVIKDK VFMDNPENAEILENIVLTLTLFEDREMIK
635


WP_024784666
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_024784894
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkVFNASYGTYHDLCKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_024786433
561
KKLRTFLDKN--FDEFRIVDIQGLDKEteTFNASYATYQDLLKVIKDK VFMDNPENAEILENIVLTLTLFEDREMIK
635


WP_049473442
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkVFNASYGTYHDLCKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


WP_049474547
561
DKLMDFLEKE--FDEFRIVDLTGLDKEnkVFNASYGTYHDLCKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
634


EMC03581
554
DKLMDFLEKE--FDEFRIVDLTGLDKEnkAFNASYGTYHDLRKIL-DK DFLDNSKNEKILEDIVLTLTLFEDREMIR
627


WP_000428612
565
KDIIQYLHT---VDGYDGIELKGIEKQ---FNASLSTYHDLLKIIKDK EFMDDPNNEEILENIVHTLTIFEDREMIK
635


WP_000428613
563
KDIIQFLHN---VDGYDGIELKGIEKQ---FNASLSTYHDLLKIIKDK EFMDDSKNEEILENIVHTLTIFEDREMIK
633


WP_049523028
562
KDIIHYLHN---VDGYDGIELKGIEKH---FNSSLSTYHDLLKIIKDK EFMDDPKNEEIFENIVHTLTIFEDRVMIK
632


WP_003107102
531
KQLKENYFNK--IRCLDSITISGVEDK---FNASLGTYHDLLNIIKNQ KILDDEQNQDSLEDIVLTLTLFEDEKMIA
602


WP_054279288
564
KQLKEDFFSK--IECFDTVDISGVEDK---FNASLGTYHDLLKIIKDK AFLDNSENENIIEDIILTLTLFEDKEMIA
635


WP_049531101
563
KDLIHYLHN---VDGYDGIELKGIEKQ---FNASLSTYHDLLKIIKDK RFMDEPKNQEILENIVHTLTIFEDREMIK
633


WP_049538452
563
KDIIQYLHN---VDGYDGIELKGIEKQ---FNASLSTYHDLLKIIKDK EFMDDSKNEEILENIVHTLTIFEDREMIK
633


WP_049549711
563
KDIIHYLHT---VDGYDGIELKGIEKQ---FNASLSTYHDLLKIIKDK EFMDDSKNEAILENIVHTLTIFEDREMIK
633


WP_007896501
565
KDLKEKYFSQ--IEGLENVDVTGVEGA---FNASLGTYNDLLKIIKDK AFLDDEANAEILEEIVLILTLFQDEKLIE
636


EFR44625
517
KDLKEKYFSQ--IEGLENVDVTGVEGA---FNASLGTYNDLLKIIKDK AFLDDEANAEILEEIVLILTLFQDEKLIE
588


WP_002897477
562
KDIIHYLHN---VDGYDGIELKGIEKQ---FNANLSTYHDLLKITKDK EFMDDPKNEEILENIVHTLTIFEDREMIK
632


WP_002906454
562
KDIIHYLHN---VDGYDGIELKGIEKQ---FNASLSTYHDLLKIIKDK EFMDNPKNGEILENIIHTLTIFEDREMIK
632


WP_009729476
563
KDIIQFLHN---VDGYDGIELKGIEKQ---FNASLSTYHDLLKIIKDK AFMDDAKNEAILENIVHTLTIFEDREMIK
633


CQR24647
562
KKILNFLDKN--FDEFRITDIQGLDNEtgNENASYGTYHDLLKIIGDK EFMDSSDNVDVLEDIVLSLTLFEDREMIK
636


WP_000066813
565
KDIIHYLHN---VDGYDGIELKGIEKQ---FNASLSTYHDLLKIIKDK AFMDDSKNEEILENIIHTLTIFEDREMIK
635


WP_009754323
563
KDIIHYLHN---VDGYDGIELKGIEKQ---FNASLSTYHDLLKIIKDK EFMDNHKNQEILENIVHTLTIFEDREMIK
633


WP_044674937
562
KDIKAYL-EN--SNGYAGVELKGLEEQ---FNASLPTYHDLLKILRDK AFIDAEENQEILEDIVLTLTLFEDREMIR
632


WP_044676715
561
EKLMDFLGKE--FDEFRIVDLLGLDKDnkSFNASLGTYHDLKKIV-SK DLLDNPENEDILENVVLTLTLFEDREMIR
634


WP_044680361
561
EKLMDFLGKE--FDEFRIVDLLGLDKDnkSFNASLGTYHDLKKIV-SK DLLDNPENEDILENVVLTLTLFEDREMIR
634


WP_044681799
562
KDIKAYL-EN--SNGYAGVELKGLEEQ---FNASLPTYHDLLKILRDK AFIDAEENQEILEDIVLTLTLFEDREMIR
632


WP_049533112
561
DKLLNYLGKE--FDEFRIVDLTGLDKEnkVENSSLGTYHDLRKIL-DK SFLDNKENEQIIEDIIQTLTLFEDREMIR
634


WP_029090905
541
TSLKKWLAEH---EHMTVSVVQGTQKEt-EFATSLQAEHREVKIF-DR ETVSNPANEEMFEKIIYWSTVFEDKKIMR
612


WP_006506696
568
KKLKNWLVNNqcCS--KDAEIKGFQKEn-QESTSLTPWIDETNIFGKI ----DQSNFDLIENIIYDLTVFEDKKIMK
637


AIT42264
562
KQLKEDYFKK--IECEDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_034440723
568
NQLVKYIENK---EQIIAPEIKGIEDS---FNSNYSTYIDLSKIPDMK --LLEKDEDEILEEIIKILTIFEDRKMRK
637


AKQ21048
562
KQLKEDYFKK--IECEDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


WP_004636532
563
KDIANYLEQ---YGYVDGTDIKGVEDK---FNASLSTYNDLAKIDGAK AYLDDPEYADVWEDIIKILTIFEDKAMRK
633


WP_002364836
570
KDIIQFYRNE--YN-TEIVTLSGLEED--QFNASFSTYQDLLKCGLTR AELDHPDNAEKLEDIIKILTIFEDRQRIR
641


WP_016631044
521
KDIIQFYRNE--YN-TEIVTLSGLEED--QFNASFSTYQDLLKCGLTR AELDHPDNAEKLEDIIKILTIFEDRQRIR
592


EMS75795
306
KKLQQFLSAN--YN-IEDAEILGVDKA---FNSSYATYHDFLDLAKPN ELLEQPEMNAMFEDIVKILTIFEDREMIR
381


WP_002373311
570
KDIIQFYRNE--YN-TEIVTLSGLEED--QFNASFSTYQDLLKCGLTR AELDHPDNAEKLEDIIKILTIFEDRQRIR
641


WP_002378009
570
KDIIQFYRNE--YN-TEIVTLSGLEED--QFNASFSTYQDLLKCGLTR AELDHPDNAEKLEDIIKILTIFEDRQRIR
641


WP_002407324
570
KDIIQFYRNE--YN-TEIVTLSGLEED--QFNASFSTYQDLLKCGLTR AELDHPDNAEKLEDIIKILTIFEDRQRIR
641


WP_002413717
570
KDIIQFYRNE--YN-TEIVTLSGLEED--QFNASFSTYQDLLKCGLTR AELDHPDNAEKLEDIIKILTIFEDRQRIR
641


WP_010775580
572
KDIIQFYRNE--YN-TEIVTLSGLEED--QFNASFSTYQDLLKCGLTR AELDHPDNAEKLEDIIKILTIFEDRQRIR
643


WP_010818269
570
KDIIQFYRNE--YN-TEIVTLSGLEED--QFNASFSTYQDLLKCGLTR AELDHPDNAEKLEDIIKILTIFEDRQRIR
641


WP_010824395
570
KDIIQFYRNE--YN-TEIVTLSGLEED--QFNASFSTYQDLLKCGLTR AELDHPDNAEKLEDIIKILTIFEDRQRIR
641


WP_016622645
570
KDIIQFYRNE--YN-TEIVTLSGLEED--QFNASFSTYQDLLKCGLTR AELDHPDNAEKLEDIIKILTIFEDRQRIR
641


WP_033624816
570
KDIIQFYRNE--YN-TEIVTLSGLEED--QFNASFSTYQDLLKCGLTR AELDHPDNAEKLEDIIKILTIFEDRQRIR
641


WP_033625576
570
KDIIQFYRNE--YN-TEIVTLSGLEED--QFNASFSTYQDLLKCGLTR AELDHPDNAEKLEDIIKILTIFEDRQRIR
641


WP_033789179
570
KDIIQFYRNE--YN-TEIVTLSGLEED--QFNASFSTYQDLLKCGLTR AELDHPDNAEKLEDIIKILTIFEDRQRIR
641


WP_002310644
567
KDLQEFLYLK--YD-IKHAELSGIEKA---FNASYTTYHDFLTMSENK QWLEDPELASMFEEIIKTLTVFEDREMIK
641


WP_002312694
568
KDLQEFLYLK--YD-IKHAELSGIEKA---FNASYTTYHDFLTMSENK QWLEDPELASMFEEIIKTLTVFEDREMIK
642


WP_002314015
568
KDLQEFLYLK--YD-IKHAELSGIEKA---FNASYTTYHDFLTMSENK QWLEDPELASMFEEIIKTLTVFEDREMIK
642


WP_002320716
568
KDLQEFLYLK--YD-IKHAELSGIEKA---FNASYTTYHDFLTMSENK QWLEDPELASMFEEIIKTLTVFEDREMIK
642


WP_002330729
567
KDLQEFLYLK--YD-IKHAELSGIEKA---FNASYTTYHDFLTMSENK QWLEDPELASMFEEIIKTLTVFEDREMIK
641


WP_002335161
568
KDLQEFLYLK--YD-IKHAELSGIEKA---FNASYTTYHDFLTMSENK QWLEDPELASMFEEIIKTLTVFEDREMIK
642


WP_002345439
568
KDLQEFLYLK--YD-IKHAELSGIEKA---FNASYTTYHDFLTMSENK QWLEDPELASMFEEIIKTLTVFEDREMIK
642


WP_034867970
562
KKLQNFLYTH--YH-IENAQIFGIEKA---FNASYSTYHDFMKLAKTN EWLEQPEMEPIFEDIVKILTIFEDRQMIK
637


WP_047937432
568
KDLQEFLYLK--YD-IKHAELSGIEKA---FNASYTTYHDFLTMSENK QWLEDPELASMFEEIIKTLTVFEDREMIK
642


WP_010720994
562
KKLQNFLYTH--YH-IENAQIFGIEKA---FNASYSTYHDFMKLAKTN EWLEQPEMEPIFEDIVKILTIFEDRQMIK
637


WP_010737004
562
KKLQNFLYTH--YH-IENAQIFGIEKA---FNASYSTYHDFMKLAKTN EWLEQPEMEPIFEDIVKILTIFEDRQMIK
637


WP_034700478
562
KKLQNFLYTH--YH-IENAQIFGIEKA---FNASYSTYHDFMKLAKTN EWLEQPEMEPIFEDIVKILTIFEDRQMIK
637


WP_007209003
564
KKLENYLRIE1---SISSPSVKGIEEQ---FNANFGTYLDLKKFDELH PYLDDEKYQDTLEEVIKVLTVFEDRSMIQ
634


WP_023519017
560
KQLRKFLELN--EQ-IDSTEIKGIETS---FNASYSTYHDLLKLS--- TLLDDPDMTTMFEEIIKILTIFEDREMIR
631


WP_010770040
564
KLLEKFLSNE--FG-LVDVAIKGIE-T--SFNAGYGTYHDFLKIGITR EQLDKEENSETLEEIVKILTVFEDRKMIR
634


WP_048604708
560
KDLSNFLRNE--YN-LDDVIIDGIE-N--KFNASFNTYHDFLKLKIDP KVLDDPANEPMFEEIVKILTIFEDRKMLR
630


WP_010750235
561
KKLQHFLSAN--YN-IEDAEILGVDKV---FNSSYATYHDFLELAKPY ELLEQPEMEEMFEDIVKIITIFEDREMVR
636


AII16583
601
KQLKEDYFKK--IECFDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
672


WP_029073316
576
NAMKKWLVKNqyFSNTDDIKIEGFQKEn-ACSTSLTPWIDFTKIFGEI ----NNSNYELIEKIIYDVTVFEDKKILR
647


WP_031589969
576
NAMKKWLVKNqyFSNTDDIKIEGFQKEn-ACSTSLTPWIDFTKIFGKI ----NESNYDFIEKIIYDVTVFEDKKILR
647


KDA45870
558
KMVIKHLKVV--MPAIRIQALKGLDNGk--FNASYGTYKDLVDMGVAP ELLNDEVNSEKWEDIIKTLTIFEGRKLIK
630


WP_039099354
579
KNIQDYLVSEk--RYASRPAITGLSDEnk-FNSRLSTYHDLKTIVGDA --VDDVDKQADLEKCIEWSTIFEDGKIYS
650


AKP02966
561
KKLTKWLIAQg---YYKNPILIGLSQKd-EFNSTLTTYLDMKKIFGSS -FMENNKNYNQIEELIEWLTIFEDKQILN
632


WP_010991369
567
KDLELFLRNM--SH-VESPTIEGLE-D--SFNSSYSTYHDLLKVGIKQ EILDNPVNTEMLENIVKILTVFEDKRMIK
637


WP_033838504
567
KDLELFLRNM--SH-VESPTIEGLE-D--SFNSSYSTYHDLLKVGIKQ EILDNPVNTEMLENIVKILTVFEDKRMIK
637


EHN60060
570
KDLELFLRNM--SH-VESPTIEGLE-D--SFNSSYSTYHDLLKVGIKQ EILDNPVNTEMLENIVKILTVFEDKRMIK
640


EFR89594
336
KDLELFLRNM--SH-VESPTIEGLE-D--SFNSSYSTYHDLLKVGIKQ EILDNPVNTEMLENIVKILTVFEDKRMIK
406


WP_038409211
567
KDLERFLYTI--NH-IESPTIEGVE-D--AFNSSFATYHDLQKGGVTQ EILDNPLNADMLEEIVKILTVFEDKRMIK
637


EFR95520
186
KDLERFLYTI--NH-IESPTIEGVE-D--AFNSSFATYHDLQKGGVTQ EILDNPLNADMLEEIVKILTVFEDKRMIK
256


WP_003723650
567
KDLELFLRNI--NH-IESPTIEGLE-D--SFNASYATYHDLLKVGMKQ EILDNPLNTEMLEDIVKILTVFEDKPMIK
637


WP_003727705
567
KDLELFLRNI--NH-IESPTIEGLE-D--SFNASYATYHDLLKVGLKQ EILDNPLNTEILEDIVKILTVFEDKRMIK
637


WP_003730785
567
KDLELFLRNI--NH-IESPTIEGLE-D--SFNASYATYHDLLKVGLKQ EILDNPLNTEILEDIVKILTVFEDKRMIK
637


WP_003733029
567
KDLELFLRNI--NQ-IESPTIEGLE-D--SFNASYATYHDLLKVGMKQ EILDNPLNTEMLEDIVKILTVFEDKRMIK
637


WP_003739838
567
KDLEQFLRNM--SH-IESPTIEGLE-D--SFNSSYATYHDLLKVGIKQ EVLENPLNTEMLEDIVKILTVFEDKRMIK
637


WP_014601172
567
KDLELFLRNI--NH-IESPTIEGLE-D--SFNASYATYHDLLKVGMKQ EILDNPLNTEMLEDIVKILTVFEDKPMIK
637


WP_023548323
567
KDLELFLRNI--NH-VESPTIEGLE-D--SFNASYATYHDLMKVGIKQ EILDNPLNTEMLEDIVKILTVFEDKRMIK
637


WP_031665337
567
KDLELFLRNI--NQ-IESPTIEGLE-D--SFNASYATYHDLLKVGMKQ EILDNPLNTEMLEDIVKILTVFEDKRMIK
637


WP_031669209
567
KDLELFLRNI--NQ-IESPTIEGLE-D--SFNASYATYHDLLKVGMKQ EILDNPLNTEMLEDIVKILTVFEDKRMIK
637


WP_033920898
567
KDLELFLRNI--NH-VESPTIEGLE-D--SFNASYATYHDLMKVGIKQ EILDNPLNTEMLEDIVKILTVFEDKRMIK
637


AKI42028
570
KDLELFLRNI--NH-IESPTIEGLE-D--SFNASYATYHDLLKVGMKQ EILDNPLNTEMLEDIVKILTVFEDKPMIK
640


AKI50529
570
KDLELFLRNI--NH-VESPTIEGLE-D--SFNASYATYHDLMKVGIKQ EILDNPLNTEMLEDIVKILTVFEDKRMIK
640


EFR83390
15
KDLELFLRNI--NQ-IESPTIEGLE-D--SFNASYATYHDLLKVGMKQ EILDNPLNTEMLEDIVKILTVFEDKRMIK
85


WP_046323366
567
KDLELFLYNM--NH-VESPTVEGVE-D--AFNSSETTYHDLQKVGVPQ EILDDPLNTEMLEEIIKILTVFEDKRMIN
637


AKE81011
578
KQLKEDYFKK--IECEDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
649


CUO82355
572
KKLKNWLVNNqcCR--KDAEIKGFQKEn-QESTSLTPWIDETNIFGKI ----DQSNFDLIEKIIYDLTVFEDKKIMK
641


WP_033162887
573
KKLKDWLVTHqyYDINEELKIEGYQKD1-QESTSLAPWIDETKIFGEI ----NASNYQLIEKIIYDISIFEDKKILK
644


AGZ01981
595
KQLKEDYFKK--IECEDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
666


AKA60242
562
KQLKEDYFKK--IECEDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


AKS40380
562
KQLKEDYFKK--IECEDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
633


4UN5_B
566
KQLKEDYFKK--IECEDSVEISGVEDR---FNASLGTYHDLLKIIKDK DFLDNEENEDILEDIVLTLTLFEDREMIE
637


WP_010922251
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWcustom character RLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFcustom character QLIHDDSL
702


WP_039695303
638
ERLQKYSDIFTANQLKKLER-RHYTGWGRLSYKLINGIRNK ENNKTILDYLI DDG---SANRNFMQLINDDTL
706


WP_045635197
633
QRLAQYDSLFDEKVIKALTR-RHYTGWGKLSAKLINGICDK QTGNTILDYLI DDG---KINRNFMQLINDDGL
701


5AXW_A
369
EELTNLNSELTQEEIEQISN1KGYTGTHNLSLKAINLILDE ---------LW -------TNDNQIAIFNRLKL
426


WP_009880683
318
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
386


WP_010922251
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_011054416
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_011284745
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_011285506
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_011527619
634
ERLKTYAHLFDDKVMKQLKR-RRYTVWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_012560673
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_014407541
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_020905136
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_023080005
634
ERLKKYANLFDDKVMKQLKR-RHYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLINDDSL
702


WP_023610282
634
ERLKKYANLFDDKVMKQLKR-RHYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLINDDSL
702


WP_030125963
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_030126706
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_031488318
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_032460140
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_032461047
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_032462016
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_032462936
634
ERLKKYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_032464890
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_033888930
459
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
527


WP_038431314
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_038432938
634
ERLKKYANLFDDKVMKQLKR-RHYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLINDDSL
702


WP_038434062
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


BAQ51233
545
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
613


KGE60162

----------------------------------------- ----------- ---------------------



KGE60856

----------------------------------------- ----------- ---------------------



WP_002989955
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_003030002
635
QRLQKYSDIFTKAQLKKLER-RHYTGWGRLSYKLINGIRNK ENKKTILDYLI DDG---YANRNFMQLINDDAL
703


WP_003065552
638
ERLQKYSDIFTADQLKKLER-RHYTGWGRLSYKLINGIRNK ENNKTILDYLI DDG---SANRNFMQLINDDTL
706


WP_001040076
633
KRLDIYKDFFTESQLKKLYR-RHYTGWGRLSAKLINGIRNK ENQKTILDYLI DDG---SANRNFMQLIKDAGL
701


WP_001040078
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


WP_001040080
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


WP_001040081
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


WP_001040083
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


WP_001040085
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


WP_001040087
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


WP_001040088
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


WP_001040089
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


WP_001040090
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


WP_001040091
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


WP_001040092
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDR ESQKTILDYLI SDG---RANRNFMQLINDDGL
704


WP_001040094
633
KRLDIYKDFFTESQLKKLYR-RHYTGWGRLSAKLINGIRNK ENQKTILDYLI DDG---SANRNFMQLIKDAGL
701


WP_001040095
633
KRLDIYKDFFTESQLKKLYR-RHYTGWERLSAKLINGIRNK ENQKTILDYLI DDG---SANRNFMQLIKDAGL
701


WP_001040096
633
KRLDIYKDFFTESQLKKLYR-RHYTGWGRLSAKLINGIRNK ENQKTILDYLI DDG---SANRNFMQLIKDAGL
701


WP_001040097
633
KRLDIYKDFFTESQLKKLYR-RHYTGWGRLSAKLINGIRNK ENQKTILDYLI DDG---SANRNFMQLIKDAGL
701


WP_001040098
633
KRLDIYKDFFTESQLKKLYR-RHYTGWGRLSAKLINGIRNK ENQKTILDYLI DDG---SANRNFMQLIKDAGL
701


WP_001040099
633
KRLDIYKDFFTESQLKKLYR-RHYTGWGRLSAKLINGIRNK ENQKTILDYLI DDG---SANRNFMQLIKDAGL
701


WP_001040100
633
KRLDIYKDFFTESQLKKLYR-RHYTGWGRLSAKLINGIRNK ENQKTILDYLI DDG---SANRNFMQLIKDAGL
701


WP_001040104
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


WP_001040105
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


WP_001040106
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI SDG---RANRNFMQLIHDDGL
704


WP_001040107
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI SDG---RANRNFMQLIHDDGL
704


WP_001040108
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI SDG---RANRNFMQLIHDDGL
704


WP_001040109
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI SDG---RANRNFMQLIHDDGL
704


WP_001040110
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI SDG---RANRNFMQLIHDDGL
704


WP_015058523
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDR ESQKTILDYLI SDG---RANRNFMQLINDDGL
704


WP_017643650
633
KRLDIYKDFFTESQLKKLYR-RHYTGWGRLSAKLINGIRNK ENQKTILDYLI DDG---SANRNFMQLIKDAGL
701


WP_017647151
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---KSNRNFMQLIHDDGL
704


WP_017648376
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---KSNRNFMQLIHDDGL
704


WP_017649527
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


WP_017771611
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI SDG---RANRNFMQLIHDDGL
704


WP_017771984
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


CFQ25032
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


CFV16040
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


KLJ37842
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


KLJ72361
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


KLL20707
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
718


KLL42645
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI SDG---RANRNFMQLIHDDGL
704


WP_047207273
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


WP_047209694
633
KRLDIYKDFFTESQLKKLYR-RHYTGWGRLSAKLINGIRNK ENQKTILDYLI DDG---SANRNFMQLIKDAGL
701


WP_050198062
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


WP_050201642
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


WP_050204027
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI SDG---RANRNFMQLIHDDGL
704


WP_050881965
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


WP_050886065
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


AHN30376
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDR ESQKIILDYLI SDG---RANRNFMQLINDDGL
704


EA078426
636
KRLENYKDLFTESQLKKLYR-RHYTGWGRLSAKLINGIRDK ESQKTILDYLI DDG---RSNRNFMQLINDDGL
704


CCW42055
636
KRLDIYKDFFTESQLKKLYR-RHYTGWGRLSAKLINGIRNK ENQKTILDYLI DDG---SANRNFMQLIKDAGL
704


WP_003041502
635
QRLQKYSDIFTKAQLKKLER-RHYTGWGRLSYKLINGIRNK ENKKTILDYLI DDG---YANRNFMQLINDDAL
703


WP_037593752
636
QRLQKYSDIFTKAQLKKLER-RHYTGWGRLSYKLINGIRNK ENKKTILDYLI DDG---YANRNFMQLINDDAL
704


WP_049516684
636
QRLQKYSDIFTTQQLKKLER-RHYTGWGRLSYKLINGIRNK ENKKTILDYLI DDG---YANRNFMQLINDDAL
704


GAD46167
635
QRLQKYSDIFTKAQLKKLER-RHYTGWGRLSYKLINGIRNK ENKKTILDYLI DDG---YANRNFMQLINDDAL
703


WP_018363470
636
QRLQKYSDIFTKQQLKKLER-RHYTGWGRLSYKLINGIRNK ENNKTILDYLI DDG---SANRNFMQLINDDAL
704


WP_003043819
644
ERLKTYAHLFDDKVMKQLKR-RHYTGWGRLSRKMINGIRDK QSGKTILDFLK -DGf---SNRNFMQLIHDDSL
712


WP_006269658
635
QRLQKYSDIFTKAQLKKLER-RHYTGWGRLSYKLINGIRNK ENKKTILDYLI DDG---YANRNFMQLINDDAL
703


WP_048800889
635
QRLQKYSDIFTKAQLKKLER-RHYTGWGRLSYKLINGIRNK ENNKTILEYLV DDG---YANRNFMQLINDDTL
703


WP_012767106
634
ERLKKYANLFDDKVMKQLKR-RHYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLINDDSL
702


WP_014612333
634
ERLKKYANLFDDKVMKQLKR-RHYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLINDDSL
702


WP_015017095
634
ERLKTYAHLFDDKVMKQLKR-RHYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFIQLIHDDSL
702


WP_015057649
634
ERLKKYANLFDDKVMKQLKR-RHYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLINDDSL
702


WP_048327215
634
ERLKTYAHLFDDKVMKQLKR-RHYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFIQLIHDDSL
702


WP_049519324
634
ERLKTYAHLFDDKVMKQLKR-RHYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFIQLIHDDSL
702


WP_012515931
634
KRLDQYAHLFDKVVLNKLER-HHYTGWGRLSGKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDSEL
702


WP_021320964
634
KRLDQYAHLFDKVVLNKLER-HHYTGWGRLSGKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDSEL
702


WP_037581760
634
KRLDQYAHLFDKVVLNKLER-HHYTGWGRLSGKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDSEL
702


WP_004232481
635
ERLQKYSDIFTSQQLKKLER-RHYTGWGRLSYKLINGIRNK ENNKTILDFLI DDG---DANRNFMQLINDDSL
703


WP_009854540
636
ERLQKYSDIFTANQLKKLER-RHYTGWGRLSYKLINGIRNK ENNKTILDYLI DDG---SANRNFMQLINDDTL
704


WP_012962174
636
QRLQKYSDIFTPQQLKKLER-RHYTGWGRLSYKLINGIRNK ENGKSILDYLI DDG---YANRNFMQLISDDTL
704


WP_039695303
638
ERLQKYSDIFTANQLKKLER-RHYTGWGRLSYKLINGIRNK ENNKTILDYLI DDG---SANRNFMQLINDDTL
706


WP_014334983
635
ERLQKYSDFFTSQQLKKLER-RHYTGWGRLSYKLINGIRNK ENNKTILDFLI DDG---HANRNFMQLINDESL
703


WP_003099269
634
RRLVKYADVFEKSVLKKLKK-RHYTGWGRLSQKLINGIKDK QTGKTILGFLK -DGv---ANRNFMQLINDSSL
702


AHY15608
634
RRLVKYADVFEKSVLKKLKK-RHYTGWGRLSQKLINGIKDK QTGKTILGFLK -DGv---ANRNFMQLINDSSL
702


AHY17476
634
RRLVKYADVFEKSVLKKLKK-RHYTGWGRLSQKLINGIKDK QTGKTILGFLK -DGv---ANRNFMQLINDSSL
702


ESR09100

----------------------------------------- ----------- ---------------------



AGM98575
634
RRLVKYADVFEKSVLKKLKK-RHYTGWGRLSQKLINGIKDK QTGKTILGFLK -DGv---ANRNFMQLINDSSL
702


ALF27331
635
KRLENYSDLLTKEQVKNLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_018372492
648
KRLSELNIPFENKIIKKLAR-KKYTGWGNLSRKLIDGIRNR ETNRTILGHLI DDGf---SNRNLMQLINDDGL
716


WP_045618028
634
QRLAHYASIFDEKVIKALTR-RHYTGWGKLSAKLINGIYDK QSKKTILDYLI DDG---EINRNFMQLINDDGL
702


WP_045635197
633
QRLAQYDSLFDEKVIKALTR-RHYTGWGKLSAKLINGICDK QTGNTILDYLI DDG---KINRNFMQLINDDGL
701


WP_002263549
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002263887
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002264920
635
KRLKNYSDLLTKEQLKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002269043
635
KRLKNYSDLLTKEQLKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002269448
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002271977
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002272766
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002273241
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002275430
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTLLDYLI DDG---NSNRNFMQLINDDAL
703


WP_002276448
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002277050
636
QRLAKYADVFDKKVIDQLAR-RHYTGWGRLSAKLLNGIRDK QSCKTIMDYLI DDA---QSNRNLMQLITDDNL
704


WP_002277364
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002279025
635
KRLKNYSDLLTKEQLKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002279859
635
KRLKNYSDLLTKEQLKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002280230
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002281696
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002282247
636
QRLAKYADVFDKKVIDQLAR-RHYTGWGRLSAKLLNGIRDK QSCKTIMDYLI DDA---QSNRNLMQLITDDNL
704


WP_002282906
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002283846
635
KRLKNYSDLLTKEQLKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002287255
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002288990
635
KRLKNYSDLLTKEQLKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002289641
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002290427
635
KRLKNYSDLLTKEQLKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002295753
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002296423
635
KRLKNYSDLLTKEQLKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002304487
645
QRLQKYSDIFTKAQLKKLER-RHYTGWGRLSYKLINGIRDK QSNKTILGYLI DDG---YSNRNFMQLINDDAL
713


WP_002305844
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002307203
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTLLDYLI DDG---NSNRNFMQLINDDAL
703


WP_002310390
635
KRLKNYSDLLTKEQLKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_002352408
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTLLDYLI DDG---NSNRNFMQLINDDAL
703


WP_012997688
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_014677909
635
KRLKNYSDLLTKEQLKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_019312892
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_019313659
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_019314093
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTLLDYLI DDG---NSNRNFMQLINDDAL
703


WP_019315370
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTLLDYLI DDG---NSNRNFMQLINDDAL
703


WP_019803776
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_019805234
635
KRLKNYSDLLTKEQLKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_024783594
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_024784288
636
QRLAKYADVFDKKVIDQLAR-RHYTGWGRLSAKLLNGIRDK QSCKTIMDYLI DDA---QSNRNLMQLITDDNL
704


WP_024784666
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_024784894
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_024786433
636
QRLAKYADVFDKKVIDQLAR-RHYTGWGRLSAKLLNGIRDK QSCKTIMDYLI DDA---QSNRNLMQLITDDNL
704


WP_049473442
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


WP_049474547
635
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
703


EMC03581
628
KRLENYSDLLTKEQVKKLER-RHYTGWGRLSAELIHGIRNK ESRKTILDYLI DDG---NSNRNFMQLINDDAL
696


WP_000428612
636
QRLAQYDSLFDEKVIKALTR-RHYTGWGKLSSKLINGIRDK QTGKTILDYLM DDG---YNNRNFMQLINDDEL
704


WP_000428613
634
QRLAQYDSLFDEKVIKALIR-RHYTGWGKLSAKLIDGICDK QTGNTILDYLI DDG---KNNRNFMQLINDDGL
702


WP_049523028
633
QRLNQYDSIFDEKVIKALTR-RHYTGWGKLSAKLINGIRDK KTSKTILDYLI DDG---YSNRNFMQLINDDGL
701


WP_003107102
603
KRLSKYESIFDPSILKKLKK-RHYTGWGRLSQKLINGIRDK QTGKTILDFLI -DGq---ANRNFMQLINDPSL
671


WP_054279288
636
NRLAVYEDLFDQNVLKQLKR-RHYTGWGRLSKQLINGMRDK HTGKTILDFLK -DGf---INRNFMQLINDDNL
704


WP_049531101
634
QRLAQYASIFDEKVIKTLTR-RHYTGWGKLSAKLINCIRDR KTGKTILDYLI DDG---YNNRNFMQLINDDGL
702


WP_049538452
634
QRLAQYDSIFDEKVIKALTR-RHYTGWGKLSAKLINGIRDK QTGKTILDYLI DDG---YSNRNFMQLINDDGL
702


WP_049549711
634
QRLAQYDSLFDKKVIKALTR-RHYTGWGKLSAKLINGICDK QTGNTILDYLI DDG---EINRNFMQLINDDGL
702


WP_007896501
637
KRLAKYANLFEKSVLKKLRK-RHYRGWGRLSRQLIDGMKDK ASGKTILDFLK -DDf---ANRNFIQLINDSSL
705


EFR44625
589
KRLAKYANLFEKSVLKKLRK-RHYRGWGRLSRQLIDGMKDK ASGKTILDFLK -DDf---ANRNFIQLINDSSL
657


WP_002897477
633
QRLAQYDTLFDEKVIKALTR-RHYTGWGKLSAKLINGIRDK QSGKTILDYLI DDD---KINRNFMQLINDDGL
701


WP_002906454
633
QRLAQYDTLFDEKVIKALTR-RHYTGWGKLSAKLINGIRDK QTGKTILEYLI DDG---DCNRNFMQLINDDGL
701


WP_009729476
634
QRLAQYDSLFDEKVIKALTR-RHYTGWGKLSAKLINGISDK QTGNTILDYLI DDG---EINRNFMQLINDDGL
702


CQR24647
637
QRLLKYEDIFSKKVIANLTR-RHYTGWGRLSAKLINGIKDK HSRKTILDYLI DDG---HSNRNFMQLINDDNL
705


WP_000066813
636
QRLAQYDSLFDEKVIKALTR-RHYTGWGKLSAKLINGIRDK KSGKTILDYLI DDG---EINRNFMQLIHDDGL
704


WP_009754323
634
QRLAQYDSIFDEKVIKALTR-RHYTGWGKLSAKLINGICDK KTGKTILDYLI DDG---YNNRNFMQLINDDGL
702


WP_044674937
633
KRLEKYKDILTEEQRKKLER-RHYTGWGRLSAKLINGILDK VTRKTILGYLI DDG---TSNRNFMQLINDDTL
701


WP_044676715
635
KRLEKYKDVLTEEQRKKLER-RHYTGWGRLSAKLINGIRDK VTRKTILDYLI DDG---TSNRNFMQLINDDTL
703


WP_044680361
635
KRLEKYKDVLTEEQRKKLER-RHYTGWGRLSAKLINGIRDK VTRKTILDYLI DDG---TSNRNFMQLINDDTL
703


WP_044681799
633
KRLEKYKDILTEEQRKKLER-RHYTGWGRLSAKLINGILDK VTRKTILGYLI DDG---TSNRNFMQLINDDTL
701


WP_049533112
635
QRLQKYSDIFTKAQLKKLER-CHYTGWGRLSYKLINGIRNK ENKKTILDYLI DDG---YANRNFMQLINDDAL
703


WP_029090905
613
RKLSEYPQLTEQQQVQLAQV--RFRGWGRLSQRLINRIKTP EDHKLSINEIL ------QTNENFMQIIRNKDY
682


WP_006506696
638
RRLKKKYALPDDKVKQILKL--KYKDWSRLSKKLLDGIVAD SV--TVLDVLE -------SRLNLMEIINDKDL
705


AIT42264
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_034440723
638
RQLMKFKDKLSEKAINQLSK-KHYTGWGQLSEKLINGIRDE QSNKTILDYLI DNGcpkNMNRNFMQLINDDTL
710


AKQ21048
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


WP_004636532
634
KQLQTYSDTLSPEILKKLER-KHYTGWGRFSKKLINGLRDE GSNKTILDYLK DEGssgPTNRNFMQLIRDNTL
706


WP_002364836
642
TQLSTFKGQFSAEVLKKLER-KHYTGWGRLSKKLINGIYDK ESGKTILGYLI DDGvskHYNRNFMQLINDSQL
714


WP_016631044
593
TQLSTFKGQFSAEVLKKLER-KHYTGWGRLSKKLINGIYDK ESGKTILDYLV DDGvskHYNRNFMQLINDSQL
665


EMS75795
382
TQLKKYQSVLGDGFEKKLVK-KHYTGWGRLSERLINGIRDK KTNKTILDYLI DDDfpyNRNRNFMQLINDDSL
454


WP_002373311
642
TQLSTFKGQFSAEVLKKLER-KHYTGWGRLSKKLINGIYDK ESGKTILDYLV DDGvskHYNRNFMQLINDSQL
714


WP_002378009
642
TQLSTFKGQFSAEVLKKLER-KHYTGWGRLSKKLINGIYDK ESGKTILDYLI DDGvskHYNRNFMQLINDSQL
714


WP_002407324
642
TQLSTFKGQFSAEVLKKLER-KHYTGWGRLSKKLINGIYDK ESGKTILDYLV DDGvskHYNRNFMQLINDSQL
714


WP_002413717
642
TQLSTFKGQFSAEVLKKLER-KHYTGWGRLSKKLINGIYDK ESGKTILDYLV DDGvskHYNRNFMQLINDSQL
714


WP_010775580
644
TQLSTFKGQFSEEVLKKLER-KHYTGWGRLSKKLINGIYDK ESGKTILDYLI DDGvskHYNRNFMQLINDSQL
716


WP_010818269
642
TQLSTFKGQFSAEVLKKLER-KHYTGWGRLSKKLINGIYDK ESGKTILGYLI DDGvskHYNRNFMQLINDSQL
714


WP_010824395
642
TQLSTFKGQFSAEVLKKLER-KHYTGWGRLSKKLINGIYDK ESGKTILDYLI DDGvskHYNRNFMQLINDSQL
714


WP_016622645
642
TQLSTFKGQFSAEVLKKLER-KHYTGWGRLSKKLINGIYDK ESGKTILDYLV DDGvskHYNRNFMQLINDSQL
714


WP_033624816
642
TQLSTFKGQFSAEVLKKLER-KHYTGWGRLSKKLINGIYDK ESGKTILDYLI DDGvskHYNRNFMQLINDSQL
714


WP_033625576
642
TQLSTFKGQFSAEVLKKLER-KHYTGWGRLSKKLINGIYDK ESGKTILDYLI DDGvskHYNRNFMQLINDSQL
714


WP_033789179
642
TQLSTFKGQFSEEVLKKLER-KHYTGWGRLSKKLINGIYDK ESGKTILDYLI DDGvskHYNRNFMQLINDSQL
714


WP_002310644
642
TRLSHHEATLGKHIIKKLTK-KHYTGWGRLSKELIQGIRDK QSNKTILDYLI DDDfphHRNRNFMQLINDDSL
714


WP_002312694
643
TRLSHHEATLGKHIIKKLTK-KHYTGWGRLSKELIQGIRDK QSNKTILDYLI DDDfphHRNRNFMQLINDDSL
715


WP_002314015
643
TRLSHHEATLGKHIIKKLTK-KHYTGWGRLSKELIQGIRDK QSNKTILDYLI DDDfphHRNRNFMQLINDDSL
715


WP_002320716
643
TRLSHHEATLGKHIIKKLTK-KHYTGWGRLSKELIQGIRDK QSNKTILDYLI DDDfphHRNRNFMQLINDDSL
715


WP_002330729
642
TRLSHHEATLGKHIIKKLTK-KHYTGWGRLSKELIQGIRDK QSNKTILDYLI DDDfphHRNRNFMQLINDDSL
714


WP_002335161
643
TRLSHHEATLGKHIIKKLTK-KHYTGWGRLSKELIQGIRDK QSNKTILDYLI DDDfphHRNRNFMQLINDDSL
715


WP_002345439
643
TRLSHHEATLGKHIIKKLTK-KHYTGWGRLSKELIQGIRDK QSNKTILDYLI DDDfphHRNRNCMQLINDDSL
715


WP_034867970
638
HQLSKYQEVFGEKLLKEFAR-KHYTGWGRFSAKLIHGIRDR KTNKTILDYLI DDDvpaNRNRNLMQLINDEHL
710


WP_047937432
643
TRLSHHEATLGKHIIKKLTK-KHYTGWGRLSKELIQGIRDK QSNKTILDYLI DDDfphHRNRNFMQLINDDSL
715


WP_010720994
638
HQLSKYQEVFGEKLLKEFAR-KHYTGWGRFSAKLIHGIRDR KTNKTILDYLI DDDvpaNRNRNLMQLINDEHL
710


WP_010737004
638
HQLSKYQEVFGEKLLKEFAR-KHYTGWGRFSAKLIHGIRDR KTNKTILDYLI DDDvpaNRNRNLMQLINDEHL
710


WP_034700478
638
HQLSKYQEVFGEKLLKEFAR-KHYTGWGRFSAKLIHGIRDR KTNKTILDYLI DDDvpaNRNRNLMQLINDEHL
710


WP_007209003
635
NQLEQLPLNLSTKTIKALSR-RKYTGWGRLSARLIDGIHDK NSGKTILDYLI DESdsyIVNRNFMQLINDDHL
707


WP_023519017
632
EQLKPYETVLGLPAIKKLAK-KHYTGWGRLSEKMIQGMREK QSRKTILDYLI DDDfpcNRNRNFMQLINDDHL
704


WP_010770040
635
EQLKKYTYLFDEEVLKKLER-RHYTGWGRLSAKLLIGIKEK RTHKTILDYLI DDGgkqPINRNLMQLINDSDL
707


WP_048604708
631
EQLSKFSDRLSEKTIKDLER-RHYTGWGRLSAKLINGIHDK QSNKTILDYLI DDApkkNINRNFMQLINDNRL
703


WP_010750235
637
TQLKKYQRILGEEIFKKLVK-KKYTGWGRLSKRLINGIRDQ KTNKTILDYLI DDDfpyNRNRNFMQLINDDHL
709


AII16583
673
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
741


WP_029073316
648
RRLKKEYDLDEEKIKKILKL--KYSGWSRLSKKLLSGIKTK RTPETVLEVME -------TNMNLMQVINDEKL
717


WP_031589969
648
RRLKKEYDLDEEKIKKILKL--KYSGWSRLSKKLLSGIKTK RTPETVLEVME -------TNMNLMQVINDEKL
717


KDA45870
631
RRLENYRDFLGEDILRKLSR-KKYTGWGRLSAKLLDGIYDK KTHKTILDCLM EDYs-----QNFMQLINDDTY
698


WP_039099354
651
AKLNEIDWLTDQQRVQLAAK--RYRGWGRLSAKLLTQIVN- ANGQRIMDLLW -------TTDNFMRIVHSE--
712


AKP02966
633
EKLHSSNYSYTSDQIKKISN-MRYKGWGRLSKKILTCITTE TNTPKSLQLSN -DLm-wTTNNNFISIISNDKY
706


WP_010991369
638
EQLQQFSDVLDGVVLKKLER-RHYTGWGRLSAKLLMGIRDK QSHLTILDYLM DDG----LNRNLMQLINDSNL
706


WP_033838504
638
EQLQQFSDVLDGVVLKKLER-RHYTGWGRLSAKLLMGIRDK QSHLTILDYLM DDG----LNRNLMQLINDSNL
706


EHN60060
641
EQLQQFSDVLDGVVLKKLER-RHYTGWGRLSAKLLMGIRDK QSHLTILDYLM DDG----LNRNLMQLINDSNL
709


EFR89594
407
EQLQQFSDVLDGVVLKKLER-RHYTGWGRLSAKLLMGIRDK QSHLTILDYLM DDG----LNRNLMQLINDSNL
475


WP_038409211
638
EQLQSFSDVLDGTILKKLER-RHYTGWGRLSAKLLTGIRDK HSHLTILDYLM DDG----LNRNLMQLINDSNL
706


EFR95520
257
EQLQSFSDVLDGTILKKLER-RHYTGWGRLSAKLLTGIRDK HSHLTILDYLM DDG----LNRNLMQLINDSNL
325


WP_003723650
638
EQLQQFSDVLDGGVLKKLER-RHYTGWGRLSAKLLVGIREK QSHLTILDYLM DDG----LNRNLMQLINDSNL
706


WP_003727705
638
EQLEQFSDVLDGVVLKKLER-RHYTGWGRLSAKLLVGIRDK QSHLTILDYLM DDG----LNRNLMQLINDSNL
706


WP_003730785
638
EQLEQFSDVLDGVVLKKLER-RHYTGWGRLSAKLLVGIRDK QSHLTILDYLM DDG----LNRNLMQLINDSNL
706


WP_003733029
638
EQLQQFSDVLDGTVLKKLER-RHYTGWGRLSAKLLVGIRDK QSHLTILDYLM DDG----LNRNLMQLINDSNL
706


WP_003739838
638
EQLQQFSDVLDGAVLKKLER-RHYTGWGRLSAKLLVGIRDK QSHLTILDYLM DDG----LNRNLMQLINDSNL
706


WP_014601172
638
EQLQQFSDVLDGGVLKKLER-RHYTGWGRLSAKLLVGIREK QSHLTILDYLM DDG----LNRNLMQLINDSNL
706


WP_023548323
638
EQLQQFSDVLDGTVLKKLER-RHYTGWGRLSAKLLVGIRDK QSHLTILDYLM DDG----LNRNLMQLINDSNL
706


WP_031665337
638
EQLQQFSDVLDGVVLKKLER-RHYTGWGRLSAKLLVGIRDK QSHLTILEYLM DDG----LNRNLMQLINDSNL
706


WP_031669209
638
EQLQQFSDVLDGTVLKKLER-RHYTGWGRLSAKLLVGIRDK QSHLTILDYLM DDG----LNRNLMQLINDSNL
706


WP_033920898
638
EQLQQFSDVLDGTVLKKLER-RHYTGWGRLSAKLLVGIRDK QSHLTILDYLM DDG----LNRNLMQLINDSNL
706


AKI42028
641
EQLQQFSDVLDGGVLKKLER-RHYTGWGRLSAKLLVGIREK QSHLTILDYLM DDG----LNRNLMQLINDSNL
709


AKI50529
641
EQLQQFSDVLDGTVLKKLER-RHYTGWGRLSAKLLVGIRDK QSHLTILDYLM DDG----LNRNLMQLINDSNL
709


EFR83390
86
EQLQQFSDVLDGVVLKKLER-RHYTGWGRLSAKLLVGIRDK QSHLTILEYLM DDG----LNRNLMQLINDSNL
154


WP_046323366
638
ERLQEFSNVLDEAVLKKLER-RHYTGWGRLSAKLLIGIRDK ESHLTILDYLM DDK----HNRNLMQLINDSNL
706


AKE81011
650
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
718


CUO82355
642
RRLKKKYALPDDKIKQILKL--KYKDWSRLSKKLLDGIVAD SV--TVLDVLE -------SRLNLMEIINDKEL
709


WP_033162887
645
RRLKKVYQLDDLLVDKILKL--NYTGWSRLSEKLLTGMTAD KA--TVLFVLE -------SNKNLMEIINDEKL
712


AGZ01981
667
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
735


AKA60242
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


AKS40380
634
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
702


4UN5_B
638
ERLKTYAHLFDDKVMKQLKR-RRYTGWGRLSRKLINGIRDK QSGKTILDFLK -DGf---ANRNFMQLIHDDSL
706


WP_010922251
703
TFKEDIQKAQVSG-QGcustom character RENQ TTQKGQKNS
777


WP_039695303
707
PFKQIIQKSQVVG-DVDD-IEAVVHDLPGSPAIKKGILQSVKIVDELVKVMG-GNPDNIVIEMARENQ TTNRGRSQS
780


WP_045635197
702
SFKEIIQKAQVIG-KTDD-VKQVVQELSGSPAIKKGILQSIKIVDELVKVMG-HAPESIVIEMARENQ TTARGKKNS
775


5AXW_A
427
VPKKVDLSQQKEI---PT---TLVDDFILSPVVKRSFIQSIKVINAIIKKYG--LPNDIIIELAREKN --------S
487


WP_009880683
387
TFKEDLQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
461


WP_010922251
703
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_011054416
703
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_011284745
703
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_011285506
703
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_011527619
703
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_012560673
703
TFKEDLQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_014407541
703
TFKEDIQKAQVSG-QGHS-LHEQIANLAGSPAIKKGILQTVKIVDELVKVMG-HKPENIVIEMARENQ TTQKGQKNS
776


WP_020905136
703
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_023080005
703
TFKEAIQKAQVSG-QGHS-LHEQIANLAGSPAIKKGILQTVKIVDELVKVMG-HKPENIVIEMARENQ TTQKGQKNS
776


WP_023610282
703
TFKEAIQKAQVSG-QGHS-LHEQIANLAGSPAIKKGILQTVKIVDELVKVMG-HKPENIVIEMARENQ TTQKGQKNS
776


WP_030125963
703
TFKEDLQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_030126706
703
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_031488318
703
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_032460140
703
TFKEDLQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_032461047
703
TFKEDLQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_032462016
703
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_032462936
703
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_032464890
703
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_033888930
528
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
602


WP_038431314
703
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_038432938
703
TFKEAIQKAQVSG-QGHS-LHEQIANLAGSPAIKKGILQTVKIVDELVKVMG-HKPENIVIEMARENQ TTQKGQKNS
776


WP_038434062
703
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKIVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


BAQ51233
614
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
688


KGE60162

-------------------------------------------------------------------- ---------



KGE60856

-------------------------------------------------------------------- ---------



WP_002989955
703
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_003030002
704
SFKEEIARAQIIG-DVDD-IANVVHDLPGSPAIKKGILQSVKIVDELVKVMG-HNPANIIIEMARENQ MTDKGRRNS
777


WP_003065552
707
PFKQIIQKSQVVG-DVDD-IEAVVHDLPGSPAIKKGILQSVKIVDELVKVMG-DNPDNIVIEMARENQ TTNRGRSQS
780


WP_001040076
702
SFKPIIDKARTGS-HSDN-LKEVIGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTAKGLSRS
775


WP_001040078
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_001040080
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_001040081
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_001040083
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_001040085
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_001040087
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_001040088
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_001040089
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_001040090
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVVG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_001040091
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_001040092
705
SFKSIISKAQSGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_001040094
702
SFKPIIDKARTGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTAKGLSRS
775


WP_001040095
702
SFKPIIDKARTGS-HLDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTAKGLSRS
775


WP_001040096
702
SFKPIIDKARTGS-HLDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTAKGLSRS
775


WP_001040097
702
SFKPIIDKARTGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTAKGLSRL
775


WP_001040098
702
SFKPIIDKARTGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTAKGLSRS
775


WP_001040099
702
SFKPIIDKARTGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTAKGLSRS
775


WP_001040100
702
SFKPIIDKARTGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTAKGLSRS
775


WP_001040104
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_001040105
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_001040106
705
SFKPIIDKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQVVVEMARENQ TTNQGRRNT
778


WP_001040107
705
SFKPIIDKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQVVVEMARENQ TTNQGRRNT
778


WP_001040108
705
SFKPIIDKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQVVVEMARENQ TTNQGRRNT
778


WP_001040109
705
SFKPIIDKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQVVVEMARENQ TTNQGRRNT
778


WP_001040110
705
SFKPIIDKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQVVVEMARENQ TTNQGRRNT
778


WP_015058523
705
SFKSIISKAQSGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_017643650
702
SFKPIIDKARTGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTAKGLSRL
775


WP_017647151
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_017648376
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_017649527
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_017771611
705
SFKPIIDKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQVVVEMARENQ TTNQGRRNT
778


WP_017771984
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


CFQ25032
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


CFV16040
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


KLJ37842
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


KLJ72361
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


KLL20707
719
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
792


KLL42645
705
SFKPIIDKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQVVVEMARENQ TTNKGRRNT
778


WP_047207273
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_047209694
702
SFKPIIDKARTGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTAKGLSRS
775


WP_050198062
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_050201642
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_050204027
705
SFKPIIDKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQVVVEMARENQ TTNQGRRNT
778


WP_050881965
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


WP_050886065
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


AHN30376
705
SFKSIISKAQSGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


EA078426
705
SFKSIISKAQAGS-HSDN-LKEVVGELAGSPAIKKGILQSLKIVDELVKVMG-YEPEQIVVEMARENQ TTNQGRRNS
778


CCW42055
705
SFKSIISKAQSGS-HSDN-LKEVVSELAGSPAIKKGILQSLKIVDELVKVMG-YKPEQIVVEMARENQ TTNQGRRNS
778


WP_003041502
704
SFKEEIAKAQIIG-DVDD-IANVVHDLPGSPAIKKGILQSVKIVDELVKVMG-HNPANIIIEMARENQ TTDRGRRNS
777


WP_037593752
705
SFKEEIARAQIIG-DVDD-IANVVHDLPGSPAIKKGILQSVKIVDELVKVMG-HNPANIIIEMARENQ TTDKGRRNS
778


WP_049516684
705
SFKEEIARAQIIG-DVDD-IANVVHDLPGSPAIKKGILQSVKIVDELVKVMG-HNPANIIIEMARENQ TTDKGRRNS
778


GAD46167
704
SFKEEIARAQIIG-DVDD-IANVVHDLPGSPAIKKGILQSVKIVDELVKVMG-HNPANIIIEMARENQ TTDKGRRNS
777


WP_018363470
705
SFKQIIQEAQVVG-DVDD-IETVVHDLPGSPAIKKGILQSVKIVDELIKVMG-DNPDNIVIEMARENQ TTNRGRSQS
778


WP_003043819
713
TFKEEIEKAQVSG-QGDS-LHEQIADLAGSPAIKKGILQTVKIVDELVKVMG-HKPENIVIEMARENQ TTTKGLQQS
786


WP_006269658
704
SFKEEIARAQIID-DVDD-IANVVHDLPGSPAIKKGILQSVKIVDELVKVMG-HNPANIIIEMARENQ TTDKGRRNS
777


WP_048800889
704
PFKQIIKDAQAID-DVDD-IELIVHDLPGSPAIKKGILQSIKIVDELVKVMG-YNPDNIVIEMARENQ TTTKGRRNS
777


WP_012767106
703
TFKEAIQKAQVSG-QGHS-LHEQIANLAGSPAIKKGILQSVKVVDELVKVMG-HKPENIVIEMARENQ TTQKGQKNS
776


WP_014612333
703
TFKEAIQKAQVSG-QGHS-LHEQIANLAGSPAIKKGILQSVKVVDELVKVMG-HKPENIVIEMARENQ TTQKGQKNS
776


WP_015017095
703
TFKEAIQKAQVSG-QGHS-LHEQIANLAGSPAIKKGILQSVKVVDELVKVMG-HKPENIVIEMARENQ TTQKGQKNS
776


WP_015057649
703
TFKEAIQKAQVSG-QGHS-LHEQIANLAGSPAIKKGILQSVKVVDELVKVMG-HKPENIVIEMARENQ TTQKGQKNS
776


WP_048327215
703
TFKEAIQKAQVSG-QGHS-LHEQIANLAGSPAIKKGILQSVKVVDELVKVMG-HKPENIVIEMARENQ TTQKGQKNS
776


WP_049519324
703
TFKEAIQKAQVSG-QGHS-LHEQIANLAGSPAIKKGILQSVKVVDELVKVMG-HKPENIVIEMARENQ TTQKGQKNS
776


WP_012515931
703
SFIDEIAKAQVIG-KTEY-SKDLVGNLAGSPAIKKGISQTIKIVDELVKIMG-YLPQQIVIEMARENQ TTAQGIKNA
776


WP_021320964
703
SFIDEIAKAQVIG-KTEY-SKDLVGNLASSPAIKKGISQTIKIVDELVKIMG-YLPQQIVIEMARENQ TTAQGIKNA
776


WP_037581760
703
SFIDEIAKAQVIG-KTEY-SKDLVGNLAGSPAIKKGISQTIKIVDELVKIMG-YLPQQIVIEMARENQ TTAQGIKNA
776


WP_004232481
704
SFKTTIQEAQVVG-DVDD-IEAVVHDLPGSPAIKKGILQSVKIVDELVKVMG-HNPQNIVIEMARENQ ITGYGRNRS
777


WP_009854540
705
PFKQIIQKSQVVG-DVDD-IEAVVHDLPGSPAIKKGILQSVKIVDELVKVMG-DNPDNIVIEMARENQ TTNRGRSQS
778


WP_012962174
705
PFKQIIKDAQIIG-DIDD-VTSVVRELPGSPAIKKGILQSVKIVDELVKVMG-HNPDNIVIEMARENQ TTNRGRNQS
778


WP_039695303
707
PFKQIIQKSQVVG-DVDD-IEAVVHDLPGSPAIKKGILQSVKIVDELVKVMG-GNPDNIVIEMARENQ TTNRGRSQS
780


WP_014334983
704
SFKTIIQEAQVVG-DVDD-IEAVVHDLPGSPAIKKGILQSVKIVDELVKVMG-DNPDNIVIEMARENQ TTGYGRNKS
777


WP_003099269
703
DFAKIIKNEQEKTiKNES-LEETIANLAGSPAIKKGILQSIKIVDEIVKIMG-QNPDNIVIEMARENQ STMQGIKNS
777


AHY15608
703
DFAKIIKNEQEKTiKNES-LEETIANLAGSPAIKKGILQSIKIVDEIVKIMG-QNPDNIVIEMARENQ STMQGIKNS
777


AHY17476
703
DFAKIIKNEQEKTiKNES-LEETIANLAGSPAIKKGILQSIKIVDEIVKIMG-QNPDNIVIEMARENQ STMQGIKNS
777


ESR09100

-------------------------------------------------------------------- ---------



AGM98575
703
DFAKIIKNEQEKTiKNES-LEETIANLAGSPAIKKGILQSIKIVDEIVKIMG-QNPDNIVIEMARENQ STMQGIKNS
777


ALF27331
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_018372492
717
DFKEIIRKAQTIE-NIDT-NQALVSSLPGSPAIKKGILQSLNIVDEIIAIMG-YAPTNIVIEMARENQ TTQKGRDNS
790


WP_045618028
703
SFKEIIQKAQVVG-KTND-VKQVVQELPGSPAIKKGILQSIKLVDELVKVMG-HAPESIVIEMARENQ TTARGKKNS
776


WP_045635197
702
SFKEIIQKAQVIG-KTDD-VKQVVQELSGSPAIKKGILQSIKIVDELVKVMG-HAPESIVIEMARENQ TTARGKKNS
775


WP_002263549
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002263887
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002264920
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002269043
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002269448
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRQNS
777


WP_002271977
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002272766
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002273241
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTKQGRRNS
777


WP_002275430
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002276448
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTKQGRRNS
777


WP_002277050
705
TFKDDIVKAQYVD-NSDD-LHQVVQSLAGSPAIKKGILQSLKIVDELVKVMG-KEPEQIVVEMARENQ TTAKGRRNS
778


WP_002277364
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002279025
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002279859
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002280230
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTKQGRRNS
777


WP_002281696
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002282247
705
TFKDDIVKAQYVD-NSDD-LHQVVQSLAGSPAIKKGILQSLKIVDELVKVMG-KEPEQIVVEMARENQ TTAKGRRNS
778


WP_002282906
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002283846
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002287255
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002288990
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002289641
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002290427
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSLAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002295753
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTKQGRRNS
777


WP_002296423
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002304487
714
SFKEEIAKAQVIG-EMDG-LNQVVSDIAGSPAIKKGILQSLKIVDELVKVMG-HNPANIVIEMARENQ TTAKGRRSS
787


WP_002305844
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTKQGRRNS
777


WP_002307203
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002310390
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSLAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_002352408
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGQRNS
777


WP_012997688
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_014677909
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_019312892
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_019313659
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_019314093
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_019315370
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_019803776
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_019805234
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSLAIKKGILQNLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_024783594
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_024784288
705
TFKDDIVKAQYVD-NSDD-LHQVVQSLAGSPAIKKGILQSLKIVDELVKVMG-KEPEQIVVEMARENQ TTAKGRRNS
778


WP_024784666
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_024784894
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_024786433
705
TFKDDIVKAQYVD-NSDD-LHQVVQSLAGSPAIKKGILQSLKIVDELVKVMG-KEPEQIVVEMARENQ TTAKGRRNS
778


WP_049473442
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


WP_049474547
704
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
777


EMC03581
697
SFKEEIAKAQVIG-ETDN-LNQVVSDIAGSPAIKKGILQSLKIVDELVKIMG-HQPENIVVEMARENQ FTNQGRRNS
770


WP_000428612
705
SFKEIIKKAQVVG-KTDD-VKQVVQELPGSPAIKKGILQSIKLVDELVKVMG-HEPESIVIEMARENQ TTARGKKNS
778


WP_000428613
703
SFKEITQKAQVVG-KTDD-VKQVVQELPGSPAIKKGILQSIKIVDELVKVMG-HTPESIVIEMARENQ TTARGKKNS
776


WP_049523028
702
SFKETIQKAQVVG-ETND-VKQVVQELPGSPAIKKGILQSIKIVDELVKVMG-HAPESVVIEMARENQ TTNKGKSKS
775


WP_003107102
672
DFASIIKEAQEKTiKSEK-LEETIANLAGSPAIKKGILQSVKIVDEVVKVMG-YEPSNIVIEMARENQ STQRGINNS
746


WP_054279288
705
SFKEEIKKAQEGG-LKDS-INDQIRDLAGSPAIKKGILQTINIVDEIVKIMG-KAPQHIVVEMARDVQ KTDIGVKQS
778


WP_049531101
703
SFKEIIQESQVVG-KPDD-VKQIVQELPGSSAIKKGILQSIKLVDELVKVMG-HDPESIVIEMARENQ TTARGKKNS
776


WP_049538452
703
SFKEIIQKAQVFG-KTND-VKQVVQELPGSPAIKKGILQSIKIVEELVKVMG-HEPESIVIEMARENQ TTTRGKKNS
776


WP_049549711
703
SFKKIIQKSQVVG-ETDD-VKQVVRELPGSPAIKKGILQSIKIVDELVKVMD-HAPESIVIEMARENQ TTARGKKNS
776


WP_007896501
706
DFEKLIDDAQKKAiKRES-LTEAVANLAGSPAIKKGILQSLKVVDEIVKVMG-HNPDNIVIEMSRENQ TTAQGLKNA
780


EFR44625
658
DFEKLIDDAQKKAiKRES-LTEAVANLAGSPAIKKGILQSLKVVDEIVKVMG-HNPDNIVIEMSRENQ TTAQGLKNA
732


WP_002897477
702
SFKEIIQKAQVVG-KTDD-VKQVVQELPGSPAIKKGILQSIKIVDELVKVMG-YALESIVIEMARENQ TTARGKKNS
775


WP_002906454
702
SFKEIIQKAQVVG-KTDD-VKQVVQEIPGSPAIKKGILQSIKIVDELVKVMG-HNPESIVIEMARENQ TTAKGKKNS
775


WP_009729476
703
SFKEIIQKAQVVG-KTND-VKQVVQELPGSPAIKKGILQSIKIVDELVKVMG-HAPESIVIEMARENQ TTARGKKNS
776


CQR24647
706
SFKDEIANSQVIG-DGDD-LHQVVQELAGSPAIKKGILQSLKIVDELVKVMG-YNPEQIVVEMARENQ TTARGRNNS
779


WP_000066813
705
SFKEIIQKAQVFG-KTND-VKQVVQELPGSPAIKKGILQSIKIVDELVKVMG-HAPESIVIEMARENQ TTARGKKNS
778


WP_009754323
703
SFKEIIQKAQVVG-KTDD-LTQVVRELSGSPAIKKGILQSIKIVDELVKIMG-YAPESIVIEMARENQ TTAKGKKNS
776


WP_044674937
702
SFVDEIRLAQGSG-EAED-YRAEVQNLAGSPAIKKGILQSLKIVDELIEVMG-YDPEHIVVEMARENQ FTNQGRRNS
775


WP_044676715
704
SFVDEIRLAQGSG-EAED-YRAEVQNLAGSPAIKKGILQSLKIVDELIEVMG-YDPEHIVVEMARENQ FTNQGRRNS
777


WP_044680361
704
SFVDEIRLAQGSG-EAED-YRAEVQNLAGSPAIKKGILQSLKIVDELIEVMG-YDPEHIVVEMARENQ FTNQGRRNS
777


WP_044681799
702
SFVDEIRLAQGSG-EAED-YRAEVQNLAGSPAIKKGILQSLKIVDELIEVMG-YDPEHIVVEMARENQ FTNQGRRNS
775


WP_049533112
704
SEKEETAKAQVIG-ETDD-LNQVVSDIAGSPAIKKGILQSLKIVDELVKVMG-YNPANIVIEMARENQ TTDKGRRNS
777


WP_029090905
683
LFKKIIEEQFENEtALLN--KQRIDELAASPANKKGIWQATKIVKELEKVLQ-QPAENIFIEFARSDE ES----KRS
752


WP_006506696
706
GYAQMIEEATSCPeDGKE-TYEEVERLAGSPALKRGIWQSLQIVEEITKVMK-CRPKYIYIEFERSEE -----KERT
776


AIT42264
703
TEKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_034440723
711
SFKEKIRKAQDIN-QVND-IKEIVKDLPGSPAIKKGIYQSIRIVDEIIRKMK-DRPKNIVIEMARENQ TTQEGKNKS
784


AKQ21048
703
TEKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


WP_004636532
707
SFKKKIEDAQTIE-DTTH-IYDTVAELPGSPAIKKGIRQALKIVEEIIDIIG-YEPENIVVEMARESQ TTKKGKDLS
780


WP_002364836
715
SFKNAIQKAQSSE-HEET-LSETVNELAGSPAIKKGIYQSLKIVDELVAIMG-YAPKRIVVEMARENQ TTSTGKRRS
788


WP_016631044
666
SFKNAIQKAQSSE-HEET-LSETVNELAGSPAIKKGIYQSLKIVDELVAIMG-YAPKRIVVEMARENQ TTSTGKRRS
739


EMS75795
455
SFKEELANELALA-GNQS-LLEVVEALLGSPAIKKGIWQTLKIVEELIEIIG-YNPKNIVVEMARENQ RT----NRS
524


WP_002373311
715
SFKNAIQKAQSSE-HEET-LSETVNELAGSPAIKKGIYQSLKIVDELVAIMG-YAPKRIVVEMARENQ TTSTGKRRS
788


WP_002378009
715
SFKNAIQKAQSSE-HEET-LSETVNELAGSPAIKKGIYQSLKIVDELVAIMG-YAPKRIVVEMARENQ TTSTGKRRS
788


WP_002407324
715
SFKNAIQKAQSSE-HEET-LSETVNELAGSPAIKKGIYQSLKIVDELVAIMG-YAPKRIVVEMARENQ TTSTGKRRS
788


WP_002413717
715
SFKNAIQKAQSSE-HEET-LSETVNELAGSPAIKKGIYQSLKIVDELVAIMG-YAPKRIVVEMARENQ TTSTGKRRS
788


WP_010775580
717
SFKNAIQKAQSSE-HEET-LSETVNELAGSPAIKKGIYQSLKIVDELVAIMG-YAPKRIVVEMARENQ TTSTGKRRS
790


WP_010818269
715
SFKNAIQKAQSSE-HEET-LSETVNELAGSPAIKKGIYQSLKIVDELVAIMG-YAPKRIVVEMARENQ TTSTGKRRS
788


WP_010824395
715
SFKNAIQKAQSSE-HEET-LSETVNELAGSPAIKKGIYQSLKIVDELVAIMG-YAPKRIVVEMARENQ TTSTGKRRS
788


WP_016622645
715
SFKNAIQKAQSSE-HEET-LSETVNELAGSPAIKKGIYQSLKIVDELVAIMG-YAPKRIVVEMARENQ TTSTGKRRS
788


WP_033624816
715
SFKNAIQKAQSSE-HEET-LSETVNELAGSPAIKKGIYQSLKIVDELVAIMG-YAPKRIVVEMARENQ TTSTGKRRS
788


WP_033625576
715
SFKNAIQKAQSSE-HEET-LSETVNELAGSPAIKKGIYQSLKIVDELVAIMG-YAPKRIVVEMARENQ TTSTGKRRS
788


WP_033789179
715
SFKNAIQKAQSSE-HEET-LSETVNELAGSPAIKKGIYQSLKIVDELVAIMG-YAPKRIVVEMARENQ TTSTGKRRS
788


WP_002310644
715
SFKKEIKKAQMIT-DTEN-LEEIVKELTGSPAIKKGILQSLKIVDEIVGIMG-YEPANIVVEMARENQ TTGRGLKSS
788


WP_002312694
716
SFKKEIKKAQMIT-DTEN-LEEIVKELTGSPAIKKGILQSLKIVDEIVGIMG-YEPANIVVEMARENQ TTGRGLKSS
789


WP_002314015
716
SFKKEIKKAQMIT-DTEN-LEEIVKELTGSPAIKKGILQSLKIVDEIVGIMG-YEPANIVVEMARENQ TTGRGLKSS
789


WP_002320716
716
SFKKEIKKAQMIT-DTEN-LEEIVKELTGSPAIKKGILQSLKIVDEIVGIMG-YEPANIVVEMARENQ TTGRGLKSS
789


WP_002330729
715
SFKKEIKKAQMIT-DTEN-LEEIVKELTGSPAIKKGILQSLKIVDEIVGIMG-YEPANIVVEMARENQ TTGRGLKSS
788


WP_002335161
716
SFKKEIKKAQMIT-DTEN-LEEIVKELTGSPAIKKGILQSLKIVDEIVGIMG-YEPANIVVEMARENQ TTGRGLKSS
789


WP_002345439
716
SFKKEIKKAQMIT-DTEN-LEEIVKELTGSPAIKKGILQSLKIVDEIVGIMG-YEPANIVVEMARENQ TTGRGLKSS
789


WP_034867970
711
SFKEEIAKATVFS-KHKS-LVDVIQDLPGSPAIKKGIWQSLKIVEELIAIIG-YKPKNIVIEMARENQ KT----HRT
780


WP_047937432
716
SFKKEIKKAQMIT-DTEN-LEEIVKELTGSPAIKKGILQSLKIVDEIVGIMG-YEPANIVVEMARENQ TTGRGLKSS
789


WP_010720994
711
SFKEEIAKATVFS-KHKS-LVDVIQDLPGSPAIKKGIWQSLKIVEELIAIIG-YKPKNIVIEMARENQ KT----HRT
780


WP_010737004
711
SFKEEIAKATVFS-KHKS-LVDVIQDLPGSPAIKKGIWQSLKIVEELIAIIG-YKPKNIVIEMARENQ KT----HRT
780


WP_034700478
711
SFKEEIAKATVFS-KHKS-LVDVIQDLPGSPAIKKGIWQSLKIVEELIAIIG-YKPKNIVIEMARENQ KT----HRT
780


WP_007209003
708
SFKKIIEDSQPYK-EQQS-AEEIVSELSGSPAIKKGILQSLKIVDELVAIMG-YKPKNIVVEMARENQ TTGRGKQNS
781


WP_023519017
705
SFKETIANELIMS-DSNV-LLDQVKAIPGSPAVKKGIWQSIKIVEEIIGIIG-KAPKNIVIEMARENQ RTSR----S
774


WP_010770040
708
SFKSEIAEAQSDM-NTED-LHEVVQNLAGSPAIKKGILQSLKIVDELVDIMG-SLPKNIVVEMARENQ TTSRGRTNS
781


WP_048604708
704
TFKEEIEKEQLKA-NSEEsLIEIVQNLAGSPAIKKGIFQSLKIVDELVEIMG-YAPTNIVVEMARENQ TTANGRRNS
778


WP_010750235
710
SFKEEIAKELTLS-DKQS-LLEVVEAIPGSPAIKKGIWQTLKIVEELIAIIG-YKPKNIVIEMARENQ TTTGGKNRS
783


AII16583
742
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
816


WP_029073316
718
GFKKTIDDANSTSvSGKF-SYAEVQELAGSPAIKRGIWQALLIVDEIKKIMK-HEPAHVYIEFARNED -----KERK
788


WP_031589969
718
GFKKTIDDANSTSvSGKF-SYAEVQELAGSPAIKRGIWQALLIVDEIKKIMK-HEPAHVYIEFARNED -----KERK
788


KDA45870
699
SFKETIKNAQVIE-KEET-LAKTVQELPGSPAIKKGILQSLEIVDEIIKVMG-YKPKSIVVEMARETQ --THGTRKR
771


WP_039099354
713
DFDKLITEANQMM-LAENdVQDVINDLYTSPQNKKALRQILLVVNDIQKAMKgQAPERILIEFAREDE VNPRLSVQR
788


AKP02966
707
DFKNYIENHNLNKnEDQN-ISNLVNDIHVSPALKRGITQSIKIVQEIVKFMG-HAPKYIFIEVTRETK TTSRGKRIQ
785


WP_010991369
707
SFKSIIEKEQVTT-ADKD-IQSIVADLAGSPAIKKGILQSLKIVDELVSVMG-YPPQTIVVEMARENQ TTGKGKNNS
780


WP_033838504
707
SFKSIIEKEQVTT-ADKD-IQSIVADLAGSPAIKKGILQSLKIVDELVSVMG-YPPQTIVVEMARENQ TTGKGKNNS
780


EHN60060
710
SFKSIIEKEQVTT-ADKD-IQSIVADLAGSPAIKKGILQSLKIVDELVSVMG-YPPQTIVVEMARENQ TTGKGKNNS
783


EFR89594
476
SFKSIIEKEQVTT-ADKD-IQSIVADLAGSPAIKKGILQSLKIVDELVSVMG-YPPQTIVVEMARENQ TTGKGKNNS
549


WP_038409211
707
SFKSIIEKEQVST-ADKG-IQSIVAELAGSPAIKKGILQSLKIVDELVGIMG-YPPQTIVVEMARENQ TTGKGKNNS
780


EFR95520
326
SFKSIIEKEQVST-ADKG-IQSIVAELAGSPAIKKGILQSLKIVDELVGIMG-YPPQTIVVEMARENQ TTGKGKNNS
399


WP_003723650
707
SFKSIIEKEQVST-TDKD-LQSIVAELAGSPAIKKGILQSLKIVDELVSIMG-YPPQTIVVEMARENQ TTGKGKNNS
780


WP_003727705
707
SFKSIIEKEQVST-TDKD-LQSIVADLAGSPAIKKGILQSLKIVDELVSIMG-YPPQTIVVEMARENQ TTGKGKNNS
780


WP_003730785
707
SFKSIIEKEQVST-TDKD-LQSIVADLAGSPAIKKGILQSLKIVDELVSIMG-YPPQTIVVEMARENQ TTGKGKNNS
780


WP_003733029
707
SFKSIIEKEQVST-TDKD-LQSIVAELAGSPAIKKGILQSLKIVDELVSVMG-YPPQTIVVEMARENQ TTNKGKNNS
780


WP_003739838
707
SFKSIIEKEQVST-TDKD-LQSIVADLAGSPAIKKGILQSLKIVDELVSIMG-YPPQTIVVEMARENQ TTVKGKNNS
780


WP_014601172
707
SFKSIIEKEQVST-TDKD-LQSIVADLAGSPAIKKGILQSLKIVDELVSIMG-YPPQTIVVEMARENQ TTGKGKNNS
780


WP_023548323
707
SFKSIIEKEQVST-ADKD-LQSIVADLAGSPAIKKGILQSLKVVEELVSVMG-YPPQTIVVEMARENQ TTNKGKNNS
780


WP_031665337
707
SFKSIIEKEQVST-TDKD-LQSIVAELAGSPAIKKGILQSLKIVDELVSIMG-YPPQTIVVEMARENQ TTGKGKNNS
780


WP_031669209
707
SFKSIIEKEQVST-ADKD-LQSIVADLAGSPAIKKGILQSLKIVDELVSVMG-YPPQTIVVEMARENQ TTNKGKNNS
780


WP_033920898
707
SFKSIIEKEQVST-ADKD-LQSIVADLAGSPAIKKGILQSLKVVEELVSVMG-YPPQTIVVEMARENQ TTNKGKNNS
780


AKI42028
710
SFKSIIEKEQVST-TDKD-LQSIVADLAGSPAIKKGILQSLKIVDELVSIMG-YPPQTIVVEMARENQ TTGKGKNNS
783


AKI50529
710
SFKSIIEKEQVST-ADKD-LQSIVADLAGSPAIKKGILQSLKVVEELVSVMG-YPPQTIVVEMARENQ TTNKGKNNS
783


EFR83390
155
SFKSIIEKEQVST-TDKD-LQSIVADLAGSPAIKKGILQSLKIVDELVSIMG-YPPQTIVVEMARENQ TTVKGKNNS
228


WP_046323366
707
SFKSIIEKEQVST-ADKD-IQSIVADLAGSPAIKKGILQSLKIVDELVGIMG-YPPQTIVVEMARENQ TTGKGKNNS
780


AKE81011
719
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
793


CUO82355
710
GYAQMIEEASSCPkDGKF-TYEEVAKLAGSPALKRGIWQSLQIVEEITKVMK-CRPKYIYIEFERSEE -----KERT
780


WP_033162887
713
GYKQIIEESNMQDiEGPF-KYDEVKKLAGSPAIKRGIWQALLVVREITKFMK-HEPSHIYIEFAREEQ -----KVRK
783


AGZ01981
736
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
810


AKA60242
703
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


AKS40380
703
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
777


4UN5_B
707
TFKEDIQKAQVSG-QGDS-LHEHIANLAGSPAIKKGILQTVKVVDELVKVMGrHKPENIVIEMARENQ TTQKGQKNS
781


WP_010922251
778

custom character

841


WP_039695303
781
QQRLKKLQNSLK PSYI E----DK--VE---NSHLQNDQLFLYYIQNGKDMYTGDEL--D--IDHLSDYDIDHI
851


WP_045635197
776
QQRYKRIEDSLK ILAS NILKENP--TD---NNQLQNDRLFLYYLQNGKDMYTGEAL--D--INQLSSYDIDHI
843


5AXW_A
488
KDAQKMINEMQK QTNE EIIRTTGk--E---NAKYLIEKIKLHDMQEGKCLYSLEAIplEd1LNNPFNYEVDHI
561


WP_009880683
462
RERMKRIEEGIK ELGS DILKEYP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
525


WP_010922251
778
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_011054416
778
RERMKRIEEGIK ELGS DILKEYP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_011284745
778
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_011285506
778
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_011527619
778
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_012560673
778
RERMKRIEEGIK ELGS DILKEYP--VE---TTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_014407541
777
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
840


WP_020905136
778
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_023080005
777
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
840


WP_023610282
777
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
840


WP_030125963
778
RERMKRIEEGIK ELGS DILKEYP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_030126706
778
RERMKRIEEGIK ELGS DILKEYP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_031488318
778
RERMKRIEEGIK ELGS DILKEYP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_032460140
778
RERMKRIEEGIK ELGS DILKEYP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_032461047
778
RERMKRIEEGIK ELGS DILKEYP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_032462016
778
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_032462936
778
RERMKRIEEGIK ELGS DILKEYP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_032464890
778
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_033888930
603
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
666


WP_038431314
778
RERMKRIEEGIK ELGS DILKEYP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_038432938
777
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
840


WP_038434062
778
RERMKRIEEGIK ELGS DILKEYP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


BAQ51233
689
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
752


KGE60162
1
------------ ---- -------------------------------------QEL--D--INRLSGYDVDHI
16


KGE60856

------------ ---- ---------------------------------------------------------



WP_002989955
778
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_003030002
778
QQRLKLLQDSLK PVNI K-----N--VE---NQQLQNDRLFLYYIQNGKDMYTGETL--D--INNLSQYDIDHI
840


WP_003065552
781
QQRLKKLQNSLK PSYI E----DK--VE---NSHLQNDQLFLYYIQNGKDMYTGDEL--D--IDHLSDYDIDHI
851


WP_001040076
776
RQRLTTLRESLA NLKS EKKPKYV--KDqveNHHLSDDRLFLYYLQNGKDMYTDDEL--D--IDNLSQYDIDHI
846


WP_001040078
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_001040080
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_001040081
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_001040083
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_001040085
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDDLSQYDIDHI
846


WP_001040087
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_001040088
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_001040089
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_001040090
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_001040091
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_001040092
779
RQRYKLLEDGVK NLAS DILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_001040094
776
RQRLTTLRESLA NLKS EKKPKYV--KDqveNHHLSDDRLFLYYLQNGKDMYTDDEL--D--IDNLSQYDIDHI
846


WP_001040095
776
RQRLTTLRESLA NLKS EKKPKYV--KDqveNHHLSDDRLFLYYLQNGKDMYTDDEL--D--IDNLSQYDIDHI
846


WP_001040096
776
RQRLTTLRESLA NLKS EKKPKYV--KDqveNHHLSDDRLFLYYLQNGKDMYTDDEL--D--IDNLSQYDIDHI
846


WP_001040097
776
RQRLTTLRESLA NLKS EKKPKYV--KDqveNHHLSDDRLFLYYLQNGKDMYTDDEL--D--IDNLSQYDIDHI
846


WP_001040098
776
RQRLTTLRESLA NLKS EKKPKYV--KDqveNHHLSDDRLFLYYLQNGKDMYTDDEL--D--IDNLSQYDIDHI
846


WP_001040099
776
RQRLTTLRESLA NLKS EKKPKYV--KDqveNHHLSDDRLFLYYLQNGKDMYTDDEL--D--IDNLSQYDIDHI
846


WP_001040100
776
RQRLTTLRESLA NLKS EKKPKYV--KDqveNHHLSDDRLFLYYLQNGKDMYTDDEL--D--IDNLSQYDIDHI
846


WP_001040104
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_001040105
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_001040106
779
RQRYKLLEEGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_001040107
779
RQRYKLLEEGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_001040108
779
RQRYKLLEEGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGETL--D--IDNLSQYDIDHI
846


WP_001040109
779
RQRYKLLEEGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_001040110
779
RQRYKLLEEGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_015058523
779
RQRYKLLEDGVK NLAS DILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_017643650
776
RQRLTTLRESLA NLKS EKKPKYV--KDqveNHHLSDDRLFLYYLQNGKDMYTDDEL--D--IDNLSQYDIDLI
846


WP_017647151
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGKAL--D--IDNLSQYDIDHI
846


WP_017648376
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGKAL--D--IDNLSQYDIDHI
846


WP_017649527
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_017771611
779
RQRYKLLEEGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_017771984
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


CFQ25032
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


CFV16040
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


KLJ37842
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


KLJ72361
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


KLL20707
793
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
860


KLL42645
779
RQRYKLLEEGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_047207273
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_047209694
776
RQRLTTLRESLA NLKS EKKPKYV--KDqveNHHLSDDRLFLYYLQNGKDMYTDDEL--D--IDNLSQYDIDHI
846


WP_050198062
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_050201642
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_050204027
779
RQRYKLLEEGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_050881965
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


WP_050886065
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


AHN30376
779
RQRYKLLEDGVK NLAS DILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDSLSQYDIDHI
846


EA078426
779
RQRYKLLDDGVK NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTGEAL--D--IDNLSQYDIDHI
846


CCW42055
779
RQRYKLLDDGVR NLAS NILKEYP--TD---NQALQNERLFLYYLQNGRDMYTEKAL--D--IDNLSQYDIDHI
846


WP_003041502
778
QQRLKLLQDSLK PVNI K-----N--VE---NQQLQNDRLFLYYIQNGKDMYTGETL--D--INNLSQYDIDHI
840


WP_037593752
779
QQRLKLLQDSLK PVNI K-----N--VE---NQQLQNDRLFLYYIQNGKDMYTGETL--D--INNLSQYDIDHI
841


WP_049516684
779
QQRLKLLQDSLK PVNI K-----N--VE---NQQLQNDRLFLYYIQNGKDMYTGETL--D--INNLSQYDIDHI
841


GAD46167
778
QQRLKLLQDSLK PVNI K-----N--VE---NQQLQNDRLFLYYIQNGKDMYTGETL--D--INNLSQYDIDHI
840


WP_018363470
779
QQRLKKLQNSLK PSYI E----DK--VE---NSHLQNDQLFLYYIQNGKDMYTGDEL--D--IDHLSDYDIDHI
849


WP_003043819
787
RERKKRIEEGIK ELES QILKENP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
850


WP_006269658
778
QQRLKLLQDSLK PVNI K-----N--VE---NQQLQNDRLFLYYIQNGKDMYTGETL--D--INNLSQYDIDHI
840


WP_048800889
778
QQRLKLLQDSLT PVSI K-----N--VE---NQQLQNDRLFLYYIQNGKDMYTGEEL--D--IHHLSDYDIDHI
840


WP_012767106
777
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
840


WP_014612333
777
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
840


WP_015017095
777
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
840


WP_015057649
777
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
840


WP_048327215
777
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
840


WP_049519324
777
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
840


WP_012515931
777
RQRMRKLEETAK KLGS NILKEHP--VD---NSQLQNDKRYLYYLQNGKDMYTGDDL--D--IDYLSSYDIDHI
840


WP_021320964
777
RQRMRKLEETAK KLGS NILKEHP--VD---NSQLQNDKRYLYYLQNGKDMYTGDDL--D--IDYLSSYDIDHI
840


WP_037581760
777
RQRMRKLEETAK KLGS NILKEHP--VD---NSQLQNDKRYLYYLQNGKDMYTGDDL--D--IDYLSSYDIDHI
840


WP_004232481
778
NQRLKRLQDSLK PSYV D----SK--VE---NSHLQNDRLFLYYIQNGKDMYTGEEL--D--IDHLSDYDIDHI
848


WP_009854540
779
QQRLKKLQSSLK PSYI E----DK--VE---NSHLQNDQLFLYYIQNGKDMYTGDEL--D--IDHLSDYDIDHI
849


WP_012962174
779
QQRLKKLQDSLK PSYI E----GK--VE---NNHLQDDRLFLYYIQNGKDMYTGDEL--D--IDHLSDYDIDHI
849


WP_039695303
781
QQRLKKLQNSLK PSYI E----DK--VE---NSHLQNDQLFLYYIQNGKDMYTGDEL--D--IDHLSDYDIDHI
851


WP_014334983
778
NQRLKRLQDSLK PSYV D----SK--VE---NSHLQNDRLFLYYIQNGKDMYTGEEL--D--IDRLSDYDIDHI
848


WP_003099269
778
RQRLRKLEEVHK NTGS KILKEYN--VS---NTQLQSDRLYLYLLQDGKDMYTGKEL--D--YDNLSQYDIDHI
841


AHY15608
778
RQRLRKLEEVHK NTGS KILKEYN--VS---NTQLQSDRLYLYLLQDGKDMYTGKEL--D--YDNLSQYDIDHI
841


AHY17476
778
RQRLRKLEEVHK NTGS KILKEYN--VS---NTQLQSDRLYLYLLQDGKDMYTGKEL--D--YDNLSQYDIDHI
841


ESR09100

------------ ---- ---------------------------------------------------------



AGM98575
778
RQRLRKLEEVHK NTGS KILKEYN--VS---NTQLQSDRLYLYLLQDGKDMYTGKEL--D--YDNLSQYDIDHI
841


ALF27331
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_018372492
791
AQRLKKIEDGIK -LGS DLLKQNP--IQd--NKDLQKEKLFLYYMQNGIDLYTGQPLncD--PDSLAFYDVDHI
857


WP_045618028
777
QQRYKRIEDALK NLAH NILKEHP--TD---NIQLQNDRLFLYYLQNGKDMYTGKSL--D--INQLSSCDIDHI
844


WP_045635197
776
QQRYKRIEDSLK ILAS NILKENP--TD---NNQLQNDRLFLYYLQNGKDMYTGEAL--D--INQLSSYDIDHI
843


WP_002263549
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002263887
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002264920
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002269043
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002269448
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002271977
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002272766
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002273241
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002275430
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002276448
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002277050
779
QQRYKRLKEAIK DLNH KILKEHP--TD---NQALQNNRLFLYYLQNGRDMYTGESL--D--INRLSDYDIDHV
846


WP_002277364
778
QQRLKGLTDSIK EFGS QILKEHP--VE---HSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002279025
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002279859
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002280230
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002281696
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002282247
779
QQRYKRLKEAIK DLNH KILKEHP--TD---NQALQNNRLFLYYLQNGRDMYTGESL--D--INRLSDYDIDHV
846


WP_002282906
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002283846
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002287255
778
QQRLKGLTDSIK EFGS QILKEHP--VE---HSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002288990
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002289641
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002290427
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002295753
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002296423
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002304487
788
QKRYKRLEEAIK DLNH KILKEHP--TD---NQALQNDRLFLYYLQNGRDMYTEDPL--D--INRLSDYDIDHI
855


WP_002305844
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002307203
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002310390
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_002352408
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_012997688
778
QQRLKGLTDSIK EFGS QILKEHP--VK---HSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_014677909
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_019312892
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_019313659
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_019314093
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_019315370
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_019803776
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_019805234
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_024783594
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_024784288
779
QQRYKRLKEAIK DLNH KILKEHP--TD---NQALQNNRLFLYYLQNGRDMYTGESL--D--INRLSDYDIDHV
846


WP_024784666
778
QQRLKGLTDSIK EFGS QILKEHP--VE---HSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_024784894
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_024786433
779
QQRYKRLKEAIK DLNH KILKEHP--TD---NQALQNNRLFLYYLQNGRDMYTGESL--D--INRLSDYDIDHV
846


WP_049473442
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


WP_049474547
778
QQRLKGLTDSIK EFGS QILKEHP--VE---NSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
841


EMC03581
771
QQRLKGLTDSIK EFGS QILKEHP--VE---HSQLQNDRLFLYYLQNGRDMYTGEEL--D--IDYLSQYDIDHI
834


WP_000428612
779
QQRYKRIEDSLK ILAS KILKEHP--TD---NIQLQNDRLFLYYLQNGRDMYTGKPL--D--INQLSSYDIDHI
846


WP_000428613
777
QQRYKRIEDALK NLAS NILKEHP--TN---NIQLQNDRLFLYYLQNGRDMYTGKPL--D--INQLSSYDIDHI
844


WP_049523028
776
QQRLKTLSDAIS ELG- NILKEHP--TD---NIQLQNDRLFLYYLQNGKDMYTGEAL--D--INQLSNYDIDHI
839


WP_003107102
747
RERLRKLEEVHK NIGS KILKEHE--IS---NAQLQSDRVYLYLLQDGKDMYTGKDL--D--FDRLSQYDIDHI
810


WP_054279288
779
RERMKRVQEVLK KLGS QLLKEHP--VE---NFQLQNERLYLYYLQNGKDMYTGEEL--S--ISNLSHYDIDHI
842


WP_049531101
777
QQRYKRIEDSLK ILAS NILKEHP--TD---NIQLQNDRLFLYYLQNGKDMYTGNPL--D--INHLSSYDIDHI
844


WP_049538452
777
QQRYKRIENSLK ILAS KILKEHP--TD---NNQLQNDRLFLYYLQNGKDMYTGEAL--D--INQLSSCDIDHI
844


WP_049549711
777
QQRYKRIEDSLK ILAS NILKENP--TD---NNQLQNDRLFLYYLQNGKDMYTGEAL--D--INQLSSYDIDHI
844


WP_007896501
781
RQRLKKIKEVHK KTGS RILEDNSerIT---NLTLQDNRLYLYLLQDGKDMYTGQDL--D--INNLSQYDIDHI
846


EFR44625
733
RQRLKKIKEVHK KTGS RILEDNSerIT---NLTLQDNRLYLYLLQDGKDMYTGQDL--D--INNLSQYDIDHI
798


WP_002897477
776
QQRYKRIEDALK NLAP NILKENP--TD---NIQLKNDRLFLYYLQNGKDMYTGKPL--D--INQLSSYDIDHI
843


WP_002906454
776
QQRYKRIEDALK NLAP NILKENP--TD---NIQLQNDRLFLYYLQNGKDMYTGKAI--D--INQLSNYDIDHI
843


WP_009729476
777
QQRYKRIEDSLK ILAS KILKEHP--TD---NIQLQNDRLFLYYLQNGKDMYTGEAL--D--INQLSSCDIDHI
844


CQR24647
780
QQRLGSLTKAIQ DFGS DILKRYP--VE---NNQLQNDQLYLYYLQNGKDMYTGDTL--D--IHNLSQYDIDHI
843


WP_000066813
779
QQRYKRIEDSLK NLAS NILKENP--TD---NIQLQNDRLFLYYLQNGRDMYTGKPL--E--INQLSNYDIDHI
846


WP_009754323
777
QQRYKRIEDALK NLAP TISKENP--TD---NIQLQNDRLFLYYLQNGKDMYTGEAL--D--INQLSSYDIDHI
844


WP_044674937
776
QQRYKKIENAIK NLNS KILKEYP--TN---NQALQNDRLFLYYLQNGKDMYTDEEL--D--IDQLSQYDIDHI
843


WP_044676715
778
QQRYKKIENAIK NLNS KILKEYP--TN---NQALQNDRLFLYYLQNGKDMYTDEEL--D--IDQLSQYDIDHI
845


WP_044680361
778
QQRYKKIENAIK NLNS KILKEYP--TN---NQALQNDRLFLYYLQNGKDMYTDEEL--D--IDQLSQYDIDHI
845


WP_044681799
776
QQRYKKIENAIK NLNS KILKEYP--TN---NQALQNDRLFLYYLQNGKDMYTDEEL--D--IDQLSQYDIDHI
843


WP_049533112
778
QQRLKLLQDSLK PVNI K-----N--VE---NQQLQNDRLFLYYIQNGKDMYTGETL--D--INNLSQYDIDHI
840


WP_029090905
753
TPRDKFIEKAYA ETDT EHLKELK---Qr--SKQLSSQRLFLYFIQNGKCMYSGEHL--D--IERLDSYEVDHI
823


WP_006506696
777
ESKIKKLENVYK DEQT SVLEELKg-FDn--TKKISSDSLFLYFTQLGKCMYSGKKL--D--IDSLDKYQIDHI
849


AIT42264
778
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_034440723
785
KARLKKIQEGLE NLDS HVEKQAL---D---EEMLKSPKYYLYCLQNGKDIYTGKDL--D--IGQLQTYDIDHI
848


AKQ21048
778
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


WP_004636532
781
KERLEKLTEAIK EFDG --VKVKD--LK---NENLRNDRLYLYYLQNGRDMYTNEPL--D--INNLSKYDIDHI
845


WP_002364836
789
IQRLKIVEKAMA EIGS NLLKEQP--TT---NEQLRDTRLFLYYMQNGKDMYTGDEL--S--LHRLSHYDIDHI
852


WP_016631044
740
IQRLKIVEKAMA EIGS NLLKEQP--TT---NEQLRDTRLFLYYMQNGKDMYTGDEL--S--LHRLSHYDIDHI
803


EMS75795
525
KPRLKALEEALK SFDS PLLKEQP--VD---NQALQKDRLYLYYLQNGKDMYTGEAL--D--IDRLSEYDIDHI
588


WP_002373311
789
IQRLKIVEKAMA EIGS NLLKEQP--TT---NEQLRDTRLFLYYMQNGKDMYTGDEL--S--LHRLSHYDIDHI
852


WP_002378009
789
IQRLKIVEKAMA EIGS NLLKEQP--TT---NEQLRDTRLFLYYMQNGKDMYTGDEL--S--LHRLSHYDIDHI
852


WP_002407324
789
IQRLKIVEKAMA EIGS NLLKEQP--TT---NEQLRDTRLFLYYMQNGKDMYTGDEL--S--LHRLSHYDIDHI
852


WP_002413717
789
IQRLKIVEKAMA EIGS NLLKEQP--TT---NEQLRDTRLFLYYMQNGKDMYTGDEL--S--LHRLSHYDIDHI
852


WP_010775580
791
IQRLKIVEKAMA EIGS NLLKEQP--TT---NEQLRDTRLFLYYMQNGKDMYTGDEL--S--LHRLSHYDIDHI
854


WP_010818269
789
IQRLKIVEKAMA EIGS NLLKEQP--TT---NEQLRDTRLFLYYMQNGKDMYTGDEL--S--LHRLSHYDIDHI
852


WP_010824395
789
IQRLKIVEKAMA EIGS NLLKEQP--TT---NEQLRDTRLFLYYMQNGKDMYTGDEL--S--LHRLSHYDIDHI
852


WP_016622645
789
IQRLKIVEKAMA EIGS NLLKEQP--TT---NEQLRDTRLFLYYMQNGKDMYTGDEL--S--LHRLSHYDIDHI
852


WP_033624816
789
IQRLKIVEKAMA EIGS NLLKEQP--TT---NEQLRDTRLFLYYMQNGKDMYTGDEL--S--LHRLSHYDIDHI
852


WP_033625576
789
IQRLKIVEKAMA EIGS NLLKEQP--TT---NEQLRDTRLFLYYMQNGKDMYTGDEL--S--LHRLSHYDIDHI
852


WP_033789179
789
IQRLKIVEKAMA EIGS NLLKEQP--TT---NEQLRDTRLFLYYMQNGKDMYTGDEL--S--LHRLSHYDIDHI
852


WP_002310644
789
RPRLKALEESLK DFGS QLLKEYP--TD---NSSLQKDRLYLYYLQNGRDMYTGAPL--D--IHRLSDYDIDHI
852


WP_002312694
790
RPRLKALEESLK DFGS QLLKEYP--TD---NSSLQKDRLYLYYLQNGRDMYTGAPL--D--IHRLSDYDIDHI
853


WP_002314015
790
RPRLKALEESLK DFGS QLLKEYP--TD---NSSLQKDRLYLYYLQNGRDMYTGAPL--D--IHRLSDYDIDHI
853


WP_002320716
790
RPRLKALEESLK DFGS QLLKEYP--TD---NSSLQKDRLYLYYLQNGRDMYTGAPL--D--IHRLSDYDIDHI
853


WP_002330729
789
RPRLKALEESLK DFGS QLLKEYP--TD---NSSLQKDRLYLYYLQNGRDMYTGAPL--D--IHRLSDYDIDHI
852


WP_002335161
790
RPRLKALEESLK DFGS QLLKEYP--TD---NSSLQKDRLYLYYLQNGRDMYTGAPL--D--IHRLSDYDIDHI
853


WP_002345439
790
RPRLKALEESLK DFGS QLLKEYP--TD---NSSLQKDRLYLYYLQNGRDMYTGAPL--D--IHRLSDYDIDHI
853


WP_034867970
781
SPRLKALENGLK QIGS TLLKEQP--TD---NKALQKERLYLYYLQNGRDMYTGEPL--E--IENLHQYEVDHI
844


WP_047937432
790
RPRLKALEESLK DFGS QLLKEYP--TD---NSSLQKDRLYLYYLQNGRDMYTGAPL--D--IHRLSDYDIDHI
853


WP_010720994
781
KPRLKALENGLK QIGS TLLKEQP--TD---NKALQKERLYLYYLQNGRDMYTGEPL--E--IENLHQYEVDHI
844


WP_010737004
781
SPRLKALENGLK QIGS TLLKEQP--TD---NKALQKERLYLYYLQNGRDMYTGEPL--E--IENLHQYEVDHI
844


WP_034700478
781
KPRLKALENGLK QIGS TLLKEQP--TD---NKALQKERLYLYYLQNGRDMYTGEPL--E--IENLHQYEVDHI
844


WP_007209003
782
KPRLKGIENGLK EFSD SVLKGSS--ID---NKQLQNDRLYLYYLQNGKDMYTGHEL--D--IDHLSTYDIDHI
845


WP_023519017
775
RPRLKALEEALK NIDS PLLKDYP--TD---NQALQKDRLYLYYLQNGKDMYTGEPL--E--IHRLSEYDIDHI
838


WP_010770040
782
NPRMKALEEAMR NLRS NLLKEYP--TD---NQALQNDRLYLYYLQNGKDMYTGLDL--S--LHNLSSYDIDHI
845


WP_048604708
779
RPRLKNLEKAID DLDS EILKKHP--VD---NKALQKDRLYLYYLQNGKDMYTNEEL--D--IHKLSTYDIDHI
842


WP_010750235
784
KPRLKSLEEALK NFDS QLLKERP--VD---NQSLQKDRLYLYYLQNGKDMYTGESL--D--IDRLSEYDIDHI
847


AII16583
817
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
880


WP_029073316
789
DSFVNQMLKLYK DFED EANKHLKg-EDa--KSKIRSERLKLYYTQMGKCMYTGKSL--D--IDRLDTYQVDHI
860


WP_031589969
789
DSFVNQMLKLYK DFED EANKHLKg-EDa--KSKIRSERLKLYYTQMGKCMYTGKSL--D--IDRLDTYQVDHI
860


KDA45870
772
EDRVQQIVKNLK ELPK ------P---S---NAELSDERKYLYCLQNGRDMYTGAPL--D--YDHLQFYDVDHI
833


WP_039099354
789
KRQVEQVYQNIS EL-- EIRNELK---D1-sNSALSNTRLFLYFMQGGRDMYTGDSL--N--IDRLSTYDIDHI
856


AKP02966
786
RLQSKLLNKANG -LVP EELKKHKn--D------LSSERIMLYFLQNGKSLYSEESL--N--INKLSDYQVDHI
858


WP_010991369
781
RPRYKSLEKAIK EFGS QILKEHP--TD---NQELRNNRLYLYYLQNGKDMYTGQDL--D--IHNLSNYDIDHI
844


WP_033838504
781
RPRYKSLEKAIK EFGS QILKEHP--TD---NQELRNNRLYLYYLQNGKDMYTGQDL--D--IHNLSNYDIDHI
844


EHN60060
784
RPRYKSLEKAIK EFGS QILKEHP--TD---NQELRNNRLYLYYLQNGKDMYTGQDL--D--IHNLSNYDIDHI
847


EFR89594
550
RPRYKSLEKAIK EFGS QILKEHP--TD---NQELKNNRLYLYYLQNGKDMYTGQDL--D--IHNLSNYDIDHI
613


WP_038409211
781
KPRFISLEKAIK EFGS QILKEHP--TD---NQCLKNDRLYLYYLQNGKDMYTGKEL--D--IHNLSNYDIDHI
844


EFR95520
400
KPRFISLEKAIK EFGS QILKEHP--TD---NQCLKNDRLYLYYLQNGKDMYTGKEL--D--IHNLSNYDIDHI
463


WP_003723650
781
KPRYKSLEKAIK EFGS QILKEHP--TD---NQELKNNRLYLYYLQNGKDMYTGQEL--D--IHNLSNYDIDHI
844


WP_003727705
781
KPRYKSLEKAIK DFGS QILKEHP--TD---NQELKNNRLYLYYLQNGKDIYTGQEL--D--IHNLSNYDIDHI
844


WP_003730785
781
KPRYKSLEKAIK DFGS QILKEHP--TD---NQELKNNRLYLYYLQNGKDIYTGQEL--D--IHNLSNYDIDHI
844


WP_003733029
781
KPRYKSLEKAIK EFGS QILKEHP--TD---NQELKNNRLYLYYLQNGKDMYTGQEL--D--IHNLSNYDIDHI
844


WP_003739838
781
RPRYKSLEKAIK EFGS QILKEHP--TD---NQELRNNRLYLYYLQNGKDMYTGQEL--D--IHNLSNYDIDHI
844


WP_014601172
781
KPRYKSLEKAIK EFGS KILKEHP--TD---NQELKNNRLYLYYLQNGKDMYTGQEL--D--IHNLSNYDIDHI
844


WP_023548323
781
KPRYKSLEKAIK EFGS QILKEHP--TD---NQELKNNRLYLYYLQNGKDMYTGQEL--D--IHNLSNYDIDHI
844


WP_031665337
781
KPRYKSLEKAIK EFGS QILKEHP--TD---NQELKNNRLYLYYLQNGKDMYTGQEL--D--IHNLSNYDIDHI
844


WP_031669209
781
KPRYKSLEKAIK EFGS QILKEHP--TD---NQELKNNRLYLYYLQNGKDMYTGQEL--D--IHNLSNYDIDHI
844


WP_033920898
781
KPRYKSLEKAIK EFGS QILKEHP--TD---NQELKNNRLYLYYLQNGKDMYTGQEL--D--IHNLSNYDIDHI
844


AKI42028
784
KPRYKSLEKAIK EFGS KILKEHP--TD---NQELKNNRLYLYYLQNGKDMYTGQEL--D--IHNLSNYDIDHI
847


AKI50529
784
KPRYKSLEKAIK EFGS QILKEHP--TD---NQELKNNRLYLYYLQNGKDMYTGQEL--D--IHNLSNYDIDHI
847


EFR83390
229
RPRYKSLEKAIK EFGS QILKEHP--TD---NQELKNNRLYLYYLQNGKDIYTGQEL--D--IHNLSNYDIDHI
292


WP_046323366
781
KPRFTSLEKAIK ELGS QILKEHP--TD---NQGLKNDRLYLYYLQNGKDMYTGQEL--D--IHNLSNYDIDHV
844


AKE81011
794
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
857


CUO82355
781
ESKIKKLENVYK DEQT SVLEELKg-FDn--TKKISSDSLFLYFTQLGKCMYSGKKL--D--IDSLDKYQIDHI
853


WP_033162887
784
ESKIAKLQKIYE NLQT QVYESLKk-EDa--KKRMETDALYLYYLQMGKSMYSGKPL--D--IDKLSTYQIDHI
855


AGZ01981
811
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
874


AKA60242
778
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDAI
841


AKS40380
778
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDHI
841


4UN5_B
782
RERMKRIEEGIK ELGS QILKEHP--VE---NTQLQNEKLYLYYLQNGRDMYVDQEL--D--INRLSDYDVDAI
845


WP_010922251
842


VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKEDNLTK
A--ERGcustom character

910


WP_039695303
852
IPQAFIKDDSIDNRVLTSSAKNRG-KSDD--VP S--LDIVRARKA-EWVRLYKSGLISKRKFDNLTKA--ERGGLTE
920


WP_045635197
844
IPQAFIKDDSLDNRVLTSSKDNRG-KSDN--VP S--IEVVQKRKA-FWQQLLDSKLISERKFNNLTKA--ERGGLDE
912


5AXW_A
562
IPRSVSFDNSFNNKVLVKQEEASK-KGNR--TP Fqy-LSSSDSKI-SYETFKKHILNLAKGKGRISKTk-KEYLLEE
632


WP_009880683
526
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWKQLLNAKLITQRKFDNLTKA--ERGGLSE
594


WP_010922251
842
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_011054416
842
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_011284745
842
VPQSFIKDDSIDNKVLTRSDKNRG-KSNN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_011285506
842
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_011527619
842
VPQSFIKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_012560673
842
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWKQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_014407541
841
VPQSFIKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
909


WP_020905136
842
VPQSFIKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_023080005
841
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
909


WP_023610282
841
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
909


WP_030125963
842
VPQSFIKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_030126706
842
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_031488318
842
VPQSFIKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWKQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_032460140
842
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWKQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_032461047
842
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWKQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_032462016
842
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_032462936
842
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWKQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_032464890
842
VPQSFIKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_033888930
667
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
735


WP_038431314
842
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_038432938
841
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
909


WP_038434062
842
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWKQLLNAKLITQRKFDNLTKA--ERGGLSE
910


BAQ51233
753
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
821


KGE60162
17
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
85


KGE60856

--------------------------------- --------------------------------------------



WP_002989955
842
VPQSFIKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_003030002
841
IPQAFIKDNSLDNRVLTRSDKNRG-KSDD--VP S--IEVVHEMKS-FWSKLLSVKLITQRKFDNLTKA--ERGGLTE
909


WP_003065552
852
IPQAFIKDDSIDNRVLTSSAKNRG-KSDD--VP S--LDIVRARKA-EWVRLYKSGLISKRKFDNLTKA--ERGGLTE
920


WP_001040076
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040078
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040080
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040081
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040083
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040085
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040087
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040088
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040089
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040090
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040091
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040092
847
VPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--IDIVKARKA-FWKKLLDAKLISQRKYDNLTKA--ERGGLTP
915


WP_001040094
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--VEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040095
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040096
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040097
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--VEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040098
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--VEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040099
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--VEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040100
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--VEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040104
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040105
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040106
847
VPQAFIKDDSIDNRVLVSSAKNRG-KSDN--VP S--IDIVKARKA-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040107
847
VPQAFIKDDSIDNRVLVSSAKNRG-KSDN--VP S--IDIVKARKA-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040108
847
VPQAFIKDDSIDNRVLVSSAKNRG-KSDN--VP S--IDIVKARKA-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040109
847
VPQAFIKDDSIDNRVLVSSAKNRG-KSDN--VP S--IDIVKARKA-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_001040110
847
VPQAFIKDDSIDNRVLVSSAKNRG-KSDN--VP S--IDIVKARKA-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_015058523
847
VPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--IDIVKARKA-FWKKLLDAKLISQRKYDNLTKA--ERGGLTP
915


WP_017643650
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--VEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_017647151
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_017648376
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_017649527
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_017771611
847
VPQAFIKDDSIDNRVLVSSAKNRG-KSDN--VP S--IDIVKARKA-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_017771984
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


CFQ25032
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


CFV16040
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


KLJ37842
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


KLJ72361
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


KLL20707
861
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
929


KLL42645
847
VPQAFIKDDSIDNRVLVSSAKNRG-KSDN--VP S--IDIVKARKA-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_047207273
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_047209694
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--VEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_050198062
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_050201642
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_050204027
847
VPQAFIKDDSIDNRVLVSSAKNRG-KSDN--VP S--IDIVKARKA-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_050881965
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_050886065
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


AHN30376
847
VPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--IDIVKARKA-FWKKLLDAKLISQRKYDNLTKA--ERGGLTP
915


EA078426
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


CCW42055
847
IPQAFIKDDSIDNRVLVSSAKNRG-KSDD--VP S--LEIVKDCKV-FWKKLLDAKLMSQRKYDNLTKA--ERGGLTS
915


WP_003041502
841
IPQAYIKDDSFDNRVLTSSSENRG-KSDN--VP S--IEVVCARKA-DWMRLRKAGLISQRKFDNLTKA--ERGGLTE
909


WP_037593752
842
IPQAFIKDNSLDNRVLTRSDKNRG-KSDD--VP S--IEVVHEMKS-FWSKLLSVKLITQRKFDNLTKA--ERGGLTE
910


WP_049516684
842
IPQAFIKDNSLDNRVLTRSDKNRG-KSDD--VP S--IEVVHEMKS-FWSKLLSVKLITQRKFDNLTKA--ERGGLTE
910


GAD46167
841
IPQAFIKDNSLDNRVLTRSDKNRG-KSDD--VP S--IEVVHEMKS-FWSKLLSVKLITQRKFDNLTKA--ERGGLTE
909


WP_018363470
850
IPQAFIKDDSIDNRVLTSSAKNRG-KSDD--VP S--LGIVRARKA-EWVRLYKSGLISKRKFDNLTKA--ERGGLTE
918


WP_003043819
851
VPQSFIKDDSIDNKVLTRSVENRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
919


WP_006269658
841
IPQAFIKDNSLDNRVLTRSDKNRG-KSDD--VP S--IEVVHEMKS-FWSKLLSVKLITQRKFDNLTKA--ERGGLTE
909


WP_048800889
841
IPQAFIKDDSIDNRVLTSSAKNRG-KSDN--VP N--LEVVCDRKA-DWIRLREAGLISQRKFDNLTKA--ERGGLTE
909


WP_012767106
841
VPQSFIKDDSIDNKILTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
909


WP_014612333
841
VPQSFIKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
909


WP_015017095
841
VPQSFIKDDSIDNKVLTRSDKNRG-KSDD--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
909


WP_015057649
841
VPQSFIKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
909


WP_048327215
841
VPQSFIKDDSIDNKVLTRSDKNRG-KSDD--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
909


WP_049519324
841
VPQSFIKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
909


WP_012515931
841
IPQSFIKNNSIDNKVLTSQGANRG-KLDN--VP S--EAIVRKMKG-YWQSLLRAGAISKQKFDNLTKA--ERGGLTQ
909


WP_021320964
841
IPQSFIKNNSIDNKVLTSQGANRG-KLDN--VP S--EAIVRKMKG-YWQSLLRAGAISKQKFDNLTKA--ERGGLTQ
909


WP_037581760
841
IPQSFIKNNSIDNKVLTSQGANRG-KLDN--VP S--EAIVRKMKG-YWQSLLRAGAISKQKFDNLTKA--ERGGLTQ
909


WP_004232481
849
IPQAFIKDNSIDNRVLTSSAKNRG-KSDD--VP S--IEIVRNRKS-YWYKLYKSGLISKRKFDNLTKA--ERGGLTE
917


WP_009854540
850
IPQAFIKDDSIDNRVLTSSAKNRG-KSDD--VP S--LDIVRARKA-EWVRLYKSGLISKRKFDNLTKA--ERGGLTE
918


WP_012962174
850
IPQAFIKDDSIDNRVLTSSAKNRG-KSDD--VP S--LDIVHDRKA-DWIRLYKSGLISKRKFDNLTKA--ERGGLTE
918


WP_039695303
852
IPQAFIKDDSIDNRVLTSSAKNRG-KSDD--VP S--LDIVRARKA-EWVRLYKSGLISKRKFDNLTKA--ERGGLTE
920


WP_014334983
849
IPQAFIKDNSIDNKVLTSSAKNRG-KSDD--VP S--IEIVRNRRS-YWYKLYKSGLISKRKFDNLTKA--ERGGLTE
917


WP_003099269
842
IPQSFIKDNSIDNTVLTTQASNRG-KSDN--VP N--IETVNKMKS-FWYKQLKSGAISQRKFDHLTKA--ERGALSD
910


AHY15608
842
IPQSFIKDNSIDNTVLTTQASNRG-KSDN--VP N--IETVNKMKS-FWYKQLKSGAISQRKFDHLTKA--ERGALSD
910


AHY17476
842
IPQSFIKDNSIDNTVLTTQASNRG-KSDN--VP N--IETVNKMKS-FWYKQLKSGAISQRKFDHLTKA--ERGALSD
910


ESR09100

--------------------------------- --------------------------------------------



AGM98575
842
IPQSFIKDNSIDNTVLTTQASNRG-KSDN--VP N--IETVNKMKS-FWYKQLKSGAISQRKFDHLTKA--ERGALSD
910


ALF27331
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_018372492
858
VPRSYIKNDSFDNKVLTTSKGNRK-KLDD--VP A--KEVVEKMEN-TWRRLHAAGLISDIKLSYLMKGe-----LTE
923


WP_045618028
845
IPQAFIKDDSLDNRVLTSSKDNRG-KSDN--VP S--LEIVQKRKA-FWQQLLDSKLISERKFNNLTKA--ERGGLDE
913


WP_045635197
844
IPQAFIKDDSLDNRVLTSSKDNRG-KSDN--VP S--IEVVQKRKA-FWQQLLDSKLISERKFNNLTKA--ERGGLDE
912


WP_002263549
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002263887
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002264920
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKG--ERGGLTD
910


WP_002269043
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002269448
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--EDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002271977
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002272766
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKP-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002273241
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002275430
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKP-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002276448
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002277050
847
IPQAFIKDNSIDNRVLTSSKANRG-KSDD--VP S--EDVVNRMRP-FWNKLLSSGLISQRKYNNLTKK--E---LTP
912


WP_002277364
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KNVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002279025
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKP-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002279859
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKG--ERGGLTD
910


WP_002280230
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002281696
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KNVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002282247
847
IPQAFIKDNSIDNRVLTSSKANRG-KSDD--VP S--EDVVNRMRP-FWNKLLSSGLISQRKYNNLTKK--E---LTL
912


WP_002282906
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002283846
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KNVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002287255
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KNVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002288990
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002289641
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002290427
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKG--ERGGLTD
910


WP_002295753
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002296423
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KNVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002304487
856
IPQAFIKDNSIDNRVLTRSDKNRG-KSDD--VP S--EEVVHKMKP-FWSKLLSAKLITQRKFDNLTKA--ERGGLTD
924


WP_002305844
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002307203
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_002310390
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKG--ERGGLTD
910


WP_002352408
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_012997688
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KNVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_014677909
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_019312892
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KNVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_019313659
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_019314093
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_019315370
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKP-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_019803776
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_019805234
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKG--ERGGLTD
910


WP_024783594
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_024784288
847
IPQAFIKDNSIDNRVLTSSKANRG-KSDD--VP S--EDVVNRMRP-FWNKLLSSGLISQRKYNNLTKK--E---LTL
912


WP_024784666
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KNVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_024784894
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_024786433
847
IPQAFIKDNSIDNRVLTSSKANRG-KSDD--VP S--EDVVNRMRP-FWNKLLSSGLISQRKYNNLTKK--E---LTL
912


WP_049473442
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKP-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


WP_049474547
842
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KDVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
910


EMC03581
835
IPQAFIKDNSIDNRVLTSSKENRG-KSDD--VP S--KNVVRKMKS-YWSKLLSAKLITQRKFDNLTKA--ERGGLTD
903


WP_000428612
847
VPQAFIKDDSLDNRVLTSLKDNRG-KSDN--VP S--LEVVEKMKT-FWQQLLDSKLISYRKFNNLTKA--ERGGLDE
915


WP_000428613
845
VPQAFIKDDSLDNRVLTSLKDNRG-KSDN--VP S--IEVVQKRKA-FWQQLLDSKLISERKFNNLTKA--ERGGLDE
913


WP_049523028
840
IPQAFIKDDSLDNRVLTSSKDNRG-KSDN--VP S--LEIVEKMKG-FWQQLLDSKLISERKFNNLTKA--ERGGLDE
908


WP_003107102
811
IPQSFIKDNSIDNIVLTSQESNRG-KSDN--VP Y--IAIVNKMKS-YWQHQLKSGAISQRKEDNLTKA--ERGGLSE
879


WP_054279288
843
IPRSFIKDDSIDNKVLTRSEHNRG-KTDN--VP S--IEVVKRMKP-YWQKLLDTKVISQRKFDNLTKA--ERGGLQE
911


WP_049531101
845
IPQAFIKDDSLDNRVLTSSKDNRG-KSDN--VP S--LEVVQKRKA-FWQQLLESKLISERKFNNLTKA--ERGGLNE
913


WP_049538452
845
IPQAFIKDDSLDNRVLTSSKENRG-KSDN--VP C--LEVVDKMKV-FWQQLLDFKLISYRKFNNLTKA--ERGGLDE
913


WP_049549711
845
IPQAFIKDDSLDNRVLTSSKDNRG-KSDN--VP S--LEVVQKRKA-FWQQLLDSKLISERKFNNLTKAerERDGLNE
915


WP_007896501
847
IPQSFIKDNSIDNLVLTTQKANRG-KSDN--VP S--IEVVRDMKDrVWRRQLANGAISRQKFDHLTKA--ERGGLAD
916


EFR44625
799
IPQSFIKDNSIDNLVLTTQKANRG-KSDN--VP S--IEVVRDMKDrVWRRQLANGAISRQKFDHLTKA--ERGGLAD
868


WP_002897477
844
IPQAFIKDDSIDNRVLTSSKDNRG-KSDN--VP S--LEVVQKRKA-FWQQLLDSKLISERKFNNLTKA--ERGGLDE
912


WP_002906454
844
IPQAFIKDDSLDNRVLTSSKDNRG-KSDN--VP S--IEVVQKRKA-FWQQLLDSKLISERKFNNLTKA--KRGGLDE
912


WP_009729476
845
IPQAFIKDDSLDNRVLTSSKDNRG-KSDN--VP S--LEVVDKMKV-FWQQLLDSKLISYRKFNNLTKA--ERGGLNE
913


CQR24647
844
IPQSFIKDNSLDNRVLTNSKSNRG-KSDN--VP S--NEVVKRMKG-FWLKQLDAKLISQRKFDNLTKA--ERGGLSA
912


WP_000066813
847
IPQAFIKDDSLDNRVLTSSKDNRG-KSDN--VP S--LEVVEKMKA-FWQQLLDSKLISERKFNNLTKAerERGGLNE
917


WP_009754323
845
IPQAFIKDDSLDNRVLTSSKDNRG-KSDN--VP S--LEVVKKRKA-FWQQLLDSKLISERKFNNLTKA--ERGGLDE
913


WP_044674937
844
IPQAFIKDDSLDNKVLTKSAKNRG-KSDD--VP S--LEIVHKKKN-FWKQLLDSQLISQRKFDNLTKA--ERGGLTN
912


WP_044676715
846
IPQAFIKDDSLDNKVLTKSAKNRG-KSDD--VP S--LEIVHKKKN-FWKQLLDSQLISQRKFDNLTKA--ERGGLTN
914


WP_044680361
846
IPQAFIKDDSLDNKVLTKSAKNRG-KSDD--VP S--LEIVHKKKN-FWKQLLDSQLISQRKFDNLTKA--ERGGLTN
914


WP_044681799
844
IPQAFIKDDSLDNKVLTKSAKNRG-KSDD--VP S--LEIVHKKKN-FWKQLLDSQLISQRKFDNLTKA--ERGGLTN
912


WP_049533112
841
IPQAFIKDDSFDNRVLTSSSENRG-KSDN--VP S--IEVVRARKA-DWMRLRKAGLISQRKFDNLTKA--ERGGLTE
909


WP_029090905
824
LPQSYIKDNSIENLALVKKVENQR-KKDS11LN S---SIINQNYS-RWEQLKNAGLIGEKKFRNLTRTk-----ITD
890


WP_006506696
850
VPQSLVKDDSEDNRVLVVPSENQR-KLDD1vVP ---FDIRDKMYR-FWKLLFDHELISPKKFYSLIKTe-----YTE
916


AIT42264
842
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_034440723
849
IPRSFITDNSEDNLVLTSSTVNRG-KLDN--VP Sp--DIVRQQKG-FWKQLLRAGLMSQRKFNNLTKGk-----LTD
914


AKQ21048
842
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
910


WP_004636532
846
IPQSFTTDNSIDNKVLVSRTKNQGnKSDD--VP S--INIVHKMKP-FWRQLHKAGLISDRKFKNLTKA--EHGGLTE
915


WP_002364836
853
IPQSFMKDDSLDNLVLVGSTENRG-KSDD--VP S--KEVVKDMKA-YWEKLYAAGLISQRKFQRLTKG--EQGGLTL
921


WP_016631044
804
IPQSFMKDDSLDNLVLVGSTENRG-KSDD--VP S--KEVVKDMKA-YWEKLYAAGLISQRKFQRLTKG--EQGGLTL
872


EMS75795
589
IPRSFIVDNSIDNKVLVSSKENRL-KMDD--VP D--QKVVIRMRR-YWEKLLRANLISERKFAYLTKLe-----LTP
654


WP_002373311
853
IPQSFMKDDSLDNLVLVGSTENRG-KSDD--VP S--KKVVKKMKA-YWEKLYAAGLISQRKFQRLTKG--EQGGLTL
921


WP_002378009
853
IPQSFMKDDSLDNLVLVGSTENRG-KSDD--VP S--KEVVKDMKA-YWEKLYAAGLISQRKFQRLTKG--EQGGLTL
921


WP_002407324
853
IPQSFMKDDSLDNLVLVGSTENRG-KSDD--VP S--KEVVKDMKA-YWEKLYAAGLISQRKFQRLTKG--EQGGLTL
921


WP_002413717
853
IPQSFMKDDSLDNLVLVGSTENRG-KSDD--VP S--KEVVKDMKA-YWEKLYAAGLISQRKFQRLTKG--EQGGLTL
921


WP_010775580
855
IPQSFMKDDSLDNLVLVGSTENRG-KSDD--VP S--KEVVKKMKA-YWEKLYAAGLISQRKFQRLTKG--EQGGLTL
923


WP_010818269
853
IPQSFMKDDSLDNLVLVGSTENRG-KSDD--VP S--KEVVKDMKA-YWEKLYAAGLISQRKFQRLTKG--EQGGLTL
921


WP_010824395
853
IPQSFMKDDSLDNLVLVGSTENRG-KSDD--VP S--KEVVKDMKA-YWEKLYAAGLISQRKFQRLTKG--EQGGLTL
921


WP_016622645
853
IPQSFMKDDSLDNLVLVGSTENRG-KSDD--VP S--KEVVKDMKA-YWEKLYAAGLISQRKFQRLTKG--EQGGLTL
921


WP_033624816
853
IPQSFMKDDSLDNLVLVGSTENRG-KSDD--VP S--KEVVKKMKA-YWEKLYAAGLISQRKFQRLTKG--EQGGLTL
921


WP_033625576
853
IPQSFMKDDSLDNLVLVGSTENRG-KSDD--VP S--KEVVKKMKA-YWEKLYAAGLISQRKFQRLTKG--EQGGLTL
921


WP_033789179
853
IPQSFMKDDSLDNLVLVGSTENRG-KSDD--VP S--KEVVKKMKA-YWEKLYAAGLISQRKFQRLTKG--EQGGLTL
921


WP_002310644
853
IPRSFTTDNSIDNKVLVSSKENRL-KKDD--VP S--EKVVKKMRS-FWYDLYSSKLISKRKLDNLTKIk-----LTE
918


WP_002312694
854
IPRSFTTDNSIDNKVLVSSKENRL-KKDD--VP S--EKVVKKMRS-FWYDLYSSKLISKRKLDNLTKIk-----LTE
919


WP_002314015
854
IPRSFTTDNSIDNKVLVSSKENRL-KKDD--VP S--EKVVKKMRS-FWYDLYSSKLISKRKLDNLTKIk-----LTE
919


WP_002320716
854
IPRSFTTDNSIDNKVLVSSKENRL-KKDD--VP S--EKVVKKMRS-FWYDLYSSKLISKRKLDNLTKIk-----LTE
919


WP_002330729
853
IPRSFTTDNSIDNKVLVSSKENRL-KKDD--VP S--EKVVKKMRS-FWYDLYSSKLISKRKLDNLTKIk-----LTE
918


WP_002335161
854
IPRSFTTDNSIDNKVLVSSKENRL-KKDD--VP S--EKVVKKMRS-FWYDLYSSKLISKRKLDNLTKIk-----LTE
919


WP_002345439
854
IPRSFTTDNSIDNKVLVSSKENRL-KKDD--VP S--EKVVKKMRS-FWYDLYSSKLISKRKLDNLTKIk-----LTE
919


WP_034867970
845
IPRSFIVDNSIDDKVLVASKQNQK-KRDD--VP K--KQIVNEQRI-FWNQLKEAKLISTKKYAYLTKIe-----LTP
910


WP_047937432
854
IPRSFTTDNSIDNKVLVSSKENRL-KKDD--VP S--EKVVKKMRS-FWYDLYSSKLISKRKLDNLTKIk-----LTE
919


WP_010720994
845
IPRSFIVDNSIDNKVLVASKQNQK-KRDD--VP K--KQIVNEQRI-FWNQLKEAKLISPKKYAYLTKIe-----LTP
910


WP_010737004
845
IPRSFIVDNSIDNKVLVASKQNQK-KRDD--VP K--KQIVNEQRI-FWNQLKEAKLISPKKYAYLTKIe-----LTP
910


WP_034700478
845
IPRSFIVDNSIDNKVLVASKQNQK-KRDD--VP N--KQIVNEQRI-FWNQLKEAKLISPKKYAYLTKIe-----LTP
910


WP_007209003
846
IPQSFLTDNSIDNRVLTTSKSNRG-KSDN--VP S--EEVVRKMDR-FWRKLLNAKLISERKYTNLTKKe-----LTE
911


WP_023519017
839
IPRSFIVDNSLDNKVLVSSKVNRG-KLDN--AP D--PLVVKRMRS-HWEKLHQAKLISDKKLANLTKQn-----LTE
904


WP_010770040
846
VPQSFTTDNSLDNRVLVSSKENRG-KKDD--VP S--KEVVQKNIT-LWETLKNSNLISQKKYDNLTKG--LRGGLTE
914


WP_048604708
843
IPQSFIVDNSLDNRVLVSSSKNRG-KLDD--VP S--KEVVKKMRA-FWESLYRSGLISKKKFDNLVKA--ESGGLSE
911


WP_010750235
848
IPRSFIVDHSLDNKVLVSSKENRL-KKDD--VP D--SKVVKRMKA-YWEKLLRANLISERKFSYLTKLe-----LTD
913


AII16583
881
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
949


WP_029073316
861
VPQSLLKDDSIDNKVLVLSSENQR-KLDDlvIP ---EMIRNKMFG-FWNKLYENKIISPKKFYSLIKSe-----YSD
927


WP_031589969
861
VPQSLLKDDSIDNKVLVLSSENQR-KLDDlvIP ---SSIRNKMYG-FWEKLFNNKIISPKKFYSLIKTe-----FNE
927


KDA45870
834
IPQSFLKDDSIENKVLTIKKENVR-KTNG--LP S--EAVIQKMGS-FWKKLLDAGAMTNKKYDNLRRN1--HGGLNE
902


WP_039099354
857
LPQSFIKDNSLDNRVLVSQRMNRS-KADQ--VP S--VELGQKMQI-QWEQMLRAGLITKKKYDNLTLNp--------
923


AKP02966
859
LPRTYIPDDSLENKALVLAKENQR-KADD11LN S---NVIDKNLE-RWTYMLNNNMMGLKKFKNLTRRv-----ITD
925


WP_010991369
845
VPQSFITDNSIDNLVLTSSAGNRE-KGDD--VP P--LEIVRKRKV-FWEKLYQGNLMSKRKFDYLTKA--ERGGLTE
913


WP_033838504
845
VPQSFITDNSIDNLVLTSSAGNRE-KGDD--VP P--LEIVRKRKV-FWEKLYQGNLMSKRKFDYLTKA--ERGGLTE
913


EHN60060
848
VPQSFITDNSIDNLVLTSSAGNRE-KGDD--VP P--LEIVRKRKV-FWEKLYQGNLMSKRKFDYLTKA--ERGGLTE
916


EFR89594
614
VPQSFITDNSIDNLVLTSSAGNRE-KGND--VP P--LEIVQKRKV-FWEKLYQGNLMSKRKFDYLTKA--ERGGLTE
682


WP_038409211
845
IPQSFITDNSIDNRVLVSSTANRE-KGDN--VP L--LEVVRKRKA-FWEKLYQAKLMSKRKFDYLTKA--ERGGLTE
913


EFR95520
464
IPQSFITDNSIDNRVLVSSTANRE-KGDN--VP L--LEVVRKRKA-FWEKLYQAKLMSKRKFDYLTKA--ERGGLTE
532


WP_003723650
845
VPQSFITDNSIDNLVLTSSAGNRE-KGGD--VP P--LEIVRKRKV-FWEKLYQGNLMSKRKFDYLTKA--ERGGLTE
913


WP_003727705
845
VPQSFITDNSIDNLVLTSSAGNRE-KGGD--VP P--LEIVRKRKV-FWEKLYQGNLMSKRKFDYLTKA--ERGGLTE
913


WP_003730785
845
VPQSFITDNSIDNLVLTSSAGNRE-KGGD--VP P--LEIVRKRKV-FWEKLYQGNLMSKRKFDYLTKA--ERGGLTE
913


WP_003733029
845
VPQSFITDNSVDNLVLTSSAGNRE-KGDN--VP P--LEIVQKRKI-FWEKLYQGNLMSKRKFDYLTKA--ERGGLTE
913


WP_003739838
845
VPQSFITDNSIDNLVLTSSAGNRE-KGDD--VP P--LEIVRKRKV-FWEKLFQGNLMSKRKFDYLTKA--ERGGLTE
913


WP_014601172
845
VPQSFITDNSIDNLVLTSSAGNRE-KGGD--VP P--LEIVRKRKV-FWEKLYQGNLMSKRKFDYLTKA--ERGGLTD
913


WP_023548323
845
VPQSFITDNSIDNLVLTSSAGNRE-KGDN--VP P--LEIVQKRKI-FWEKLYQGNLMSKRKFDYLTKA--ERGGLTE
913


WP_031665337
845
VPQSFITDNSIDNLVLTSSAGNRE-KGGD--VP P--LEIVRKRKV-FWEKLYQGNLMSKRKFDYLTKA--ERGGLTE
913


WP_031669209
845
VPQSFITDNSVDNLVLTSSAGNRE-KGDN--VP P--LEIVQKRKI-FWEKLYQGNLMSKRKFDYLTKA--ERGGLTE
913


WP_033920898
845
VPQSFITDNSIDNLVLTSSAGNRE-KGDN--VP P--LEIVQKRKI-FWEKLYQGNLMSKRKFDYLTKA--ERGGLTE
913


AKI42028
848
VPQSFITDNSIDNLVLTSSAGNRE-KGGD--VP P--LEIVRKRKV-FWEKLYQGNLMSKRKFDYLTKA--ERGGLTD
916


AKI50529
848
VPQSFITDNSIDNLVLTSSAGNRE-KGDN--VP P--LEIVQKRKI-FWEKLYQGNLMSKRKFDYLTKA--ERGGLTE
916


EFR83390
293
VPQSFITDNSIDNLVLTSSAGNRE-KGDD--VP P--LEIVRKRKV-FWEKLYQGNLMSKRKFDYLTKA--ERGGLTE
361


WP_046323366
845
VPQSFITDNSIDNRVLASSAANRE-KGDN--VP S--LEVVRKRKV-YWEKLYQAKLMSKRKFDYLTKA--ERGGLTE
913


AKE81011
858
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
926


CUO82355
854
VPQSLVKDDSFDNRVLVLPSENQR-KLDD1vVP ---FDIRDKMYR-FWKLLFDHELISPKKFYSLIKTe-----YTE
920


WP_033162887
856
LPQSLIKDDSFDNRVLVLPEENQW-KLDSetVP ---FEIRNKMIG-FWQMLHENGLMSNKKFFSLIRTd-----FSD
922


AGZ01981
875
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
943


AKA60242
842
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
910


AKS40380
842
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
910


4UN5_B
846
VPQSFLKDDSIDNKVLTRSDKNRG-KSDN--VP S--EEVVKKMKN-YWRQLLNAKLITQRKFDNLTKA--ERGGLSE
914


WP_010922251
911

custom character

981


WP_039695303
921
AD KAGFIKRQLVETRQITKHVAQILDARFNTEHDENDKVIR--DVKVITLKSNLVSQFRKDF EFYKVREINDY
991


WP_045635197
913
RD KVGFIKRQLVETRQITKHVAQILDARYNTEVNEKDKKNR--TVKIITLKSNLVSNERKEF RLYKVREINDY
983


5AXW_A
633
RD QKDFINRNLVDTRYATRGLMNLLRSYFR---------VNn1DVKVKSINGGFTSFLRRKW KFKKERNKGYK
702


WP_009880683
595
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVRVITLKSKLVSDERKDF QFYKVREINNY
665


WP_010922251
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
981


WP_011054416
911
LD KVGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVRVITLKSKLVSDERKDF QFYKVREINNY
981


WP_011284745
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
981


WP_011285506
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
981


WP_011527619
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
981


WP_012560673
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVRVITLKSKLVSDERKDF QFYKVREINNY
981


WP_014407541
910
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
980


WP_020905136
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
981


WP_023080005
910
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
980


WP_023610282
910
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
980


WP_030125963
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
981


WP_030126706
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
981


WP_031488318
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
981


WP_032460140
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVRVITLKSKLVSDERKDF QFYKVREINNY
981


WP_032461047
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVRVITLKSKLVSDERKDF QFYKVREINNY
981


WP_032462016
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
981


WP_032462936
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVRVITLKSKLVSDERKDF QFYKVREINNY
981


WP_032464890
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
981


WP_033888930
736
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
806


WP_038431314
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
981


WP_038432938
910
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
980


WP_038434062
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
981


BAQ51233
822
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
892


KGE60162
86
LD KVGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVRVITLKSKLVSDERKDF QFYKVREINNY
156


KGE60856

-- ------------------------------------------------------------ -----------



WP_002989955
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
981


WP_003030002
910
ED KAGFIKRQLVETRQITKHVAQILDERFNTEFDGNKRRIR--NVKIITLKSNLVSNFRKEF ELYKVREINDY
980


WP_003065552
921
AD KAGFIKRQLVETRQITKHVAQILDARFNTESDENDKVIR--DVKVITLKSNLVSQFRKDF EFYKVREINDY
991


WP_001040076
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF VFYKIREVNNY
986


WP_001040078
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNDY
986


WP_001040080
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040081
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040083
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040085
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040087
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040088
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040089
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040090
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040091
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040092
916
DD KAGFIQRQLVETRQITKHVARILDERFNNKVDDNNKPIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040094
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040095
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040096
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040097
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040098
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040099
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040100
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040104
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040105
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_001040106
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNDY
986


WP_001040107
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNDY
986


WP_001040108
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNDY
986


WP_001040109
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNDY
986


WP_001040110
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNDY
986


WP_015058523
916
DD KAGFIQRQLVETRQITKHVARILDERFNNKVDDNNKPIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_017643650
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_017647151
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_017648376
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_017649527
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_017771611
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNDY
986


WP_017771984
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


CFQ25032
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


CFV16040
916
DD KARFIQRQLVEIRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


KLJ37842
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTVKSNLVSNFRKEF GFYKIREVNNY
986


KLJ72361
916
DD KARFIQRQLVETRQITKHVARILDELFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


KLL20707
930
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
1000


KLL42645
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNDY
986


WP_047207273
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_047209694
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_050198062
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_050201642
916
DD KARFIQRQLVETRQITKHVASILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_050204027
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNDY
986


WP_050881965
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


WP_050886065
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


AHN30376
916
DD KAGFIQRQLVETRQITKHVARILDERFNNKVDDNNKPIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


EA078426
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNNY
986


CCW42055
916
DD KARFIQRQLVETRQITKHVARILDERFNNELDSKGRRIR--KVKIVTLKSNLVSNFRKEF GFYKIREVNDY
986


WP_003041502
910
ND KAGFIKRQLVETRQITKHVAQVLDARFNAKHDENKKVIR--DVKIITLKSNLVSQFRKDF KFYKVREINDY
980


WP_037593752
911
ED KAGFIKRQLVETRQITKHVAQILDERFNTEFDGAQRRIR--NVKIITLKSNLVSNFRKEF ELYKVREINDY
981


WP_049516684
911
ED KAGFIKRQLVETRQITKHVAQILDERFNTEFDGAQRRIR--NVKIITLKSNLVSNFRKEF ELYKVREINDY
981


GAD46167
910
ED KAGFIKRQLVETRQITKHVAQILDERFNTEFDGAQRRIR--NVKIITLKSNLVSNFRKEF ELYKVREINDY
980


WP_018363470
919
AD KAGFIKRQLVETRQITKHVAQILDARFNTERDENDKVIR--DVKVITLKSNLVSQFRKEF KFYKVREINDY
989


WP_003043819
920
AD KAGFIKRQLVETRQITKHVARILDSRMNTKRDKNDKPIR--EVKVITLKSKLVSDFRKDF QLYKVRDINNY
990


WP_006269658
910
ED KAGFIKRQLVETRQITKHVAQILDERFNTEFDGNKRRIR--NVKIITLKSNLVSNFRKEF ELYKVREINDY
980


WP_048800889
910
ND KAGFIHRQLVETRQITKHVAQILDARFNPKRDDNKKVIR--DVKIITLKSNLVSQFRRDF KLYKVREINDY
980


WP_012767106
910
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDFRKDF QFYKVREINNY
980


WP_014612333
910
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDFRKDF QFYKVREINNY
980


WP_015017095
910
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDFRKDF QFYKVREINNY
980


WP_015057649
910
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDFRKDF QFYKVREINNY
980


WP_048327215
910
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDFRKDF QFYKVREINNY
980


WP_049519324
910
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDFRKDF QFYKVREINNY
980


WP_012515931
910
VD KAGFIQRQLVETRQITKHVAQILDSRFNTEFDDHNKRIR--KVHIITLKSKLVSDFRKEF GLYKIRDINHY
980


WP_021320964
910
VD KAGFIQRQLVETRQITKHVAQILDSRFNTEFDDHNKRIR--KVHIITLKSKLVSDFRKEF GLYKIRDINHY
980


WP_037581760
910
VD KAGFIQLQLVETRQITKHVAQILDSRFNTEFDDHNKRIR--KVHIITLKSKLVSDFRKEF GLYKIRDINHY
980


WP_004232481
918
TD KAGFIKRQLVETRQITKHVAQILDARFNTKCDENDKVIR--DVKVITLKSSLVSQFRKEF KFYKVREINDY
988


WP_009854540
919
AD KAGFIKRQLVETRQITKHVAQILDARFNTEHDENDKVIR--DVKVITLKSNLVSQFRKDF EFYKVREINDY
989


WP_012962174
919
ND KAGFIKRQLVETRQITKHVAQILDSRFNTERDENDKVIR--NVKVITLKSNLVSQFRKDF KFYKVREINDY
989


WP_039695303
921
AD KAGFIKRQLVETRQITKHVAQILDARFNTEHDENDKVIR--DVKVITLKSNLVSQFRKDF EFYKVREINDY
991


WP_014334983
918
AD KAGFIKRQLVETRQITKHVAQILDARFNTKRDENDKVIR--DVKVITLKSNLVSQFRKEF KFYKVREINDY
988


WP_003099269
911
FD KAGFIKRQLVETRQITKHVAQILDSRFNSNLTEDSKSNR--NVKIITLKSKMVSDFRKDF GFYKLREVNDY
981


AHY15608
911
FD KAGFIKRQLVETRQITKHVAQILDSRFNSNLTEDSKSNR--NVKIITLKSKMVSDFRKDF GFYKLREVNDY
981


AHY17476
911
FD KAGFIKRQLVETRQITKHVAQILDSRFNSNLTEDSKSNR--NVKIITLKSKMVSDFRKDF GFYKLREVNDY
981


ESR09100

-- ------------------------------------------------------------ -----------



AGM98575
911
FD KAGFIKRQLVETRQITKHVAQILDSRFNSNLTEDSKSNR--NVKIITLKSKMVSDFRKDF GFYKLREVNDY
981


ALF27331
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_018372492
924
ED KAGFIRRQLVETRQITKHVARLLDEKLNRKKNENGEKLR--TTKIITLKSVFASRFRANF DLYKLRELNHY
994


WP_045618028
914
RD KVGFIKRQLVETRQITKHVAQILDARFNTEVTEKDKKDR--SVKIITLKSNLVSNFRKEF RLYKVREINDY
984


WP_045635197
913
RD KVGFIKRQLVETRQITKHVAQILDARYNTEVNEKDKKNR--TVKIITLKSNLVSNFRKEF RLYKVREINDY
983


WP_002263549
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002263887
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002264920
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002269043
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002269448
911
DD KAGFIKRQLVETRQITKHVARILDERFYTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002271977
911
DD KAGFIKRQLVETRQITKHVARILDERFYTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002272766
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002273241
911
DD KAGFIKRQLVETRQITKHVARILDERFYTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002275430
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002276448
911
DD KAGFIKRQLVETRQITKHVARILDERFYTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002277050
913
DD KAGFIKRQLVETRQITKHVARMLDERFNKEFDDNNKRIR--RVKIVTLKSNLVSSFRKEF ELYKVREINDY
983


WP_002277364
911
DD KAGFIKRQLVETRQITKHVARILDERFHTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002279025
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002279859
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002280230
911
DD KAGFIKRQLVETRQITKHVARILDERFYTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002281696
911
DD KAGFIKRQLVETRQITKHVARILDERFHTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002282247
913
DD KAGFIKRQLVETRQITKHVARMLDERFNKEFDDNNKRIR--RVKIVTLKSNLVSSFRKEF ELYKVREINDY
983


WP_002282906
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002283846
911
DD KAGFIKRQLVETRQITKHVARILDERFHTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002287255
911
DD KAGFIKRQLVETRQITKHVARILDERFHTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002288990
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002289641
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002290427
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002295753
911
DD KAGFIKRQLVETRQITKHVARILDERFYTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002296423
911
DD KAGFIKRQLVETRQITKHVARILDERFHTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002304487
925
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
995


WP_002305844
911
DD KAGFIKRQLVETRQITKHVARILDERFYTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002307203
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002310390
911
DD KAGFIKHQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_002352408
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_012997688
911
DD KAGFIKRQLVETRQITKHVARILDERFHTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_014677909
911
DD KAGFIKRQLVETRQITKHVARILDERFYTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_019312892
911
DD KAGFIKRQLVETRQITKHVARILDERFHTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_019313659
911
DD KAGFIKRQLVETRQITKHVARILDERFHTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_019314093
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_019315370
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_019803776
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_019805234
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_024783594
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_024784288
913
DD KAGFIKRQLVETRQITKHVARMLDERFNKEFDDNNKRIR--RVKIVTLKSNLVSSFRKEF ELYKVREINDY
983


WP_024784666
911
DD KAGFIKRQLVETRQITKHVARILDERFHTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_024784894
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_024786433
913
DD KAGFIKRQLVETRQITKHVARMLDERFNKEFDDNNKRIR--RVKIVTLKSNLVSSFRKEF ELYKVREINDY
983


WP_049473442
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


WP_049474547
911
DD KAGFIKRQLVETRQITKHVARILDERFNTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
981


EMC03581
904
DD KAGFIKRQLVETRQITKHVARILDERFHTETDENNKKIR--QVKIVTLKSNLVSNFRKEF ELYKVREINDY
974


WP_000428612
916
RD KVGFIKRQLVETRQITKHVAQILDARYNTEVNEKDKKNR--TVKIITLKSNLVSNFRKEF RLYKIREINDY
986


WP_000428613
914
RD KVGFIKRQLVETRQITKHVAQILDARFNKEVNEKDKKNR--TVKIITLKSNLVSNFRKEF RLYKVREINDY
984


WP_049523028
909
RD KVGFIKRQLVETRQITKHVAQILDDRFNAEVNEKNQKLR--SVKIITLKSNLVSNFRKEF GLYKVREINDY
979


WP_003107102
880
YD KAGFIKRQLVETRQITKHVAQILNNRFNNNVDDSSKNKR--PVKIITLKSKMVSDFRKEF GFYKIREVNDY
950


WP_054279288
912
SD KANFIQRQLVETRQITKHVAQILDSRFNTERDEKDRPIR--RVKVITLKSKFVSDFRQDF GFYKLREINDY
982


WP_049531101
914
RD KVGFIKRQLVETRQITKHVAQILDSRFNTKVNEKNQKIR--TVKIITLKSNLVSNFRKEF RLYKVREINDY
984


WP_049538452
914
RD KVGFIRRQLVETRQITKHVAQILDSRFNTEVTEKDKKNR--NVKIITLKSNLVSNFRKEF GLYKVREINDY
984


WP_049549711
916
LD KVGFIKRQLVETRQITKHVAQILDARFNKEVTEKDKKNR--NVKIITLKSNLVSNFRKEF RLYKVREINDY
986


WP_007896501
917
SD KARFLRRQLVETRQITKHVAQLLDSRFNSKSNQNKKLAR--NVKIITLKSKIVSDFRKDF GLYKLREVNNY
987


EFR44625
869
SD KARFLRRQLVETRQITKHVAQLLDSRFNSKSNQNKKLAR--NVKIITLKSKIVSDFRKDF GLYKLREVNNY
939


WP_002897477
913
RD KVGFIRRQLVETQQITKNVAQILDARFNTEVKEKNQKIR--TVKIITLKSNLVSNFRKEF GLYKVREINNY
983


WP_002906454
913
RD KVGFIKRQLVETRQITKHVAQLLDTRENTEVNEENQKIR--TVKIITLKSNLVSNFRKEF GLYKVREINDY
983


WP_009729476
914
LD KVGFIKRQLVETRQITKHVAQILDARFNKEVTEKDKKNR--TVKIITLKSNLVSNFRKEF ELYKVREINDY
984


CQR24647
913
ED KAGFIKRQLVETRQITKHVARILDERFNRDFDKNDKRIR--NVKIVTLKSNLVSNFRKEF GFYKVREINNF
983


WP_000066813
918
LD KVGFIKRQLVETRQITKHVAQFLDARFNKEVTEKDKKNR--NVKIITLKSNLVSNFRKEF GLYKVREINDY
988


WP_009754323
914
RD KVGFIKRQLVETRQITKHVARILDARENTEVSEKNQKIR--SVKIITLKSNLVSNFRKEF KLYKVREINDY
984


WP_044674937
913
ED KARFIQRQLVETRQITKHVARILDTRENTKLDEAGNRIRdpKVNIITLKSNLVSQFRKDY QLYKVREINNY
985


WP_044676715
915
ED KARFIQRQLVETRQITKHVARILDTRENTKLDEAGNRIRdpKVNIITLKSNLVSQFRKDY QLYKVREINNY
987


WP_044680361
915
ED KARFIQRQLVETRQITKHVARILDTRENTKLDEAGNRIRdpKVNIITLKSNLVSQFRKDY QLYKVREINNY
987


WP_044681799
913
ED KARFIQRQLVETRQITKHVARILDTRENTKLDEAGNRIRdpKVNIITLKSNLVSQFRKDY QLYKVREINNY
985


WP_049533112
910
ND KAGFIKRQLVETRQITKHVAQVLDARFNAKHDENKKVIR--DVKIITLKSNLVSQFRKDF KFYKVREINDY
980


WP_029090905
891
RD KEGFIARQLVETRQITKHVTQLLQQEY-----------K-dTTKVFAIKATLVSGLRRKF EFIKNRNVNDY
951


WP_006506696
917
RD EERFINRQLVETRQITKNVTQIIEDHYST-------------TKVAAIRANLSHEFRVKN HIYKNRDINDY
976


AIT42264
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
981


WP_034440723
915
RD RQQFINRQLVETRQITKHVANLLSHHLNEK-----KEVG--EINIVLLKSALTSQFRKKE DFYKVREVNDY
980


AKQ21048
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
981


WP_004636532
916
AD RAHFLNRQLVETRQITKHVANLLDSQYNTAEEQ-----R---INIVLLKSSMTSRFRKEF KLYKVREINDY
980


WP_002364836
922
ED KAHFIQRQLVETRQITKNVAGILDQRYNANSKE-----K--KVQIITLKASLTSQFRSIF GLYKVREVNDY
987


WP_016631044
873
ED KAHFIQRQLVETRQITKNVAGILDQRYNAKSKE-----K--KVQIITLKASLTSQFRSIF GLYKVREVNDY
938


EMS75795
655
ED KARFIQRQLVETRQITKHVAAILDQYFN-QPEE-SK-NK--GIRIITLKSSLVSQFRKTF GINKVREINNH
722


WP_002373311
922
ED KAHFIQRQLVETRQITKNVAGILDQRYNAKSKE-----K--KVQIITLKASLTSQFRSIF GLYKVREVNDY
987


WP_002378009
922
ED KAHFIQRQLVETRQITKNVAGILDQRYNAKSKE-----K--KVQIITLKASLTSQFRSIF GLYKVREVNDY
987


WP_002407324
922
ED KAHFIQRQLVETRQITKNVAGILDQRYNAKSKE-----K--KVQIITLKASLTSQFRSIF GLYKVREVNDY
987


WP_002413717
922
ED KAHFIQRQLVETRQITKNVAGILNQRYNANSKE-----K--KVQIITLKASLTSQFRSIF GLYKVREVNDY
987


WP_010775580
924
ED KAHFIQRQLVETRQITKNVAGILDQRYNAKSKE-----K--KVQIITLKASLTSQFRSIF GLYKVREVNDY
989


WP_010818269
922
ED KAHFIQRQLVETRQITKNVAGILDQRYNAKSKE-----K--KVQIITLKASLTSQFRSIF GLYKVREVNDY
987


WP_010824395
922
ED KAHFIQRQLVETRQITKNVAGILDQLYNAKSKE-----K--KVQIITLKASLTSQFRSIF GLYKVREVNDY
987


WP_016622645
922
ED KAHFIQRQLVETRQITKNVAGILDQRYNAKSKE-----K--KVQIITLKASLTSQFRSIF GLYKVREVNDY
987


WP_033624816
922
ED KAHFIQRQLVETRQITKNVAGILDQRYNAKSKE-----K--KVQIITLKASLTSQFRSIF GLYKVREVNDY
987


WP_033625576
922
ED KAHFIQRQLVETRQITKNVAGILDQRYNAKSKE-----K--KVQIITLKASLTSQFRSIF GLYKVREVNDY
987


WP_033789179
922
ED KAHFIQRQLVETRQITKNVAGILDQRYNAKSKE-----K--KVQIITLKASLTSQFRSIF GLYKVREVNDY
987


WP_002310644
919
ED KAGFIKRQLVETRQITKHVAGILHHREN-KAEDTNEPIR--KVRIITLKSALVSQFRNRF GIYKVREINEY
988


WP_002312694
920
ED KAGFIKRQLVETRQITKHVAGILHHREN-KAEDTNDPIR--KVRIITLKSALVSQFRNRF GIYKVREINEY
989


WP_002314015
920
ED KAGFIKRQLVETRQITKHVAGILHHREN-KAEDTNEPIR--KVRIITLKSALVSQFRNRF GIYKVREINEY
989


WP_002320716
920
ED KAGFIKRQLVETRQITKHVAGILHHREN-KAEDTNEPIR--KVRIITLKSALVSQFRNRF GIYKVREINEY
989


WP_002330729
919
ED KAGFIKRQLVETRQITKHVAGILHHRFN-KAEDTNEPIR--KVRIITLKSALVSQFRNRF GIYKVREINEY
988


WP_002335161
920
ED KAGFIKRQLVETRQITKHVAGILHHRFN-KAEDTNEPIR--KVRIITLKSALVSQFRNRF GIYKVREINEY
989


WP_002345439
920
ED KAGFIKRQLVETRQITKHVAGILHHRFN-KAEDTNEPIR--KVRIITLKSALVSQFRNRF GIYKVREINEY
989


WP_034867970
911
ED KARFIQRQLVETRQITKHVANILHQSFN-QEEEGTD-CD--GVQIITLKATLTSQFRQTF GLYKVREINPH
979


WP_047937432
920
ED KAGFIKRQLVETRQITKHVAGILHHRFN-KAEDTNEPIR--KVRIITLKSALVSQFRNRF GIYKVREINEY
989


WP_010720994
911
ED KARFIQRQLVETRQITKHVANILHQSFN-QEEEGTD-CD--GVQIITLKATLTSQFRQTF GLYKVREINPH
979


WP_010737004
911
ED KARFIQRQLVETRQITKHVANILHQSFN-QEEEGTD-CD--GVQIITLKATLTSQFRQTF GLYKVREINPH
979


WP_034700478
911
ED KARFIQRQLVETRQITKHVANILHQSFN-QEEEGTD-CD--GVQIITLKATLTSQFRQTF GLYKVREINPH
979


WP_007209003
912
SD KAGFLKRQLVETRQITKHVATILDSKFNE--DSNNRDVQ-----IITLKSALVSEFRKTF NLYKVREINDL
977


WP_023519017
905
AD KARFIQRQLVETRQITKHVANLLHQHFN-LPEEVSA-TE--KTSIITLKSTLTSQFRQMF DIYKVREINHH
973


WP_010770040
915
DD RAHFIKRQLVETRQITKHVARILDQRFNSQKDEEGKTIR--AVRVVTLKSSLTSQFRKQF AIHKVREINDY
985


WP_048604708
912
DD KAGFIHRQLVETRQITKNVARILHQRFNSEKDEEGNLIR--KVRIITLKSALTSQFRKNY GIYKIREINDY
982


WP_010750235
914
DD KARFIQRQLVETRQITKHVAAILHQYFN-QTQELEK-EK--DIRIITLKSSLVSQFRQVF GIHKVREINHH
982


AII16583
950
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDERKDF QFYKVREINNY
1020


WP_029073316
928
KD KERFINRQIVETRQITKHVAQIISNHYET-------------TKVVTVRADLSHAFRERY HIYKNRDINDF
987


WP_031589969
928
KD QERFINRQIVETRQITKHVAQIIDNHYEN-------------TKVVTVRADLSHQFRERY HIYKNRDINDF
987


KDA45870
903
KL KERFIERQLVETRQITKYVAQLLDQRLN--YDGNGVELD-eKIAIVTLKAQLASQFRSEF KLRKVRALNNL
972


WP_039099354
924
-D MKGFINRQLVETRQVIKLATNLLMEQYGED-----------NIELITVKSGLTHQMRTEF DFPKNRNLNNH
990


AKP02966
926
KD KLGFIHRQLVQTSQMVKGVANILNSMYK---NQGTTCIQ--------ARANLSTAFRKAL ELVKNRNINDF
999


WP_010991369
914
AD KARFIHRQLVETRQITKNVANILHQRFNYEKDDHGNTMK--QVRIVTLKSALVSQFRKQF QLYKVRDVNDY
984


WP_033838504
914
AD KARFIHRQLVETRQITKNVANILHQRFNYEKDDHGNTMK--QVRIVTLKSALVSQFRKQF QLYKVRDVNDY
984


EHN60060
917
AD KARFIHRQLVETRQITKNVANILHQRFNYEKDDHGNTMK--QVRIVTLKSALVSQFRKQF QLYKVRDVNDY
987


EFR89594
683
AD KARFIHRQLVETRQITKNVANILHQRFNYGKDDHGNTMK--QVRIVTLKSALVSQFRKQF QLYKVRGVNDY
753


WP_038409211
914
AD KANFIQRQLVETRQITKNVANILYQRFNCKQDENGNEVE--QVRIVTLKSTLVSQFRKQF QLYKVREVNDY
984


EFR95520
533
AD KANFIQRQLVETRQITKNVANILYQRFNCKQDENGNEVE--QVRIVTLKSTLVSQFRKQF QLYKVREVNDY
603


WP_003723650
914
AD KARFIHRQLVETRQITKNVANILYQRFNKETDNHGNTME--QVRIVTLKSALVSQFRKQF QLYKVREVNGY
984


WP_003727705
914
AD KARFIHRQLVETRQITKNVANILHQRFNKETDNHGNTME--QVRIVTLKSALVSQFRKQF QLYKVREVNDY
984


WP_003730785
914
AD KARFIHRQLVETRQITKNVANILHQRFNKETDNHGNTME--QVRIVTLKSALVSQFRKQF QLYKVREVNDY
984


WP_003733029
914
AD KARFIHRQLVETRQITKNVANILHQRFNYKTDGNKDTME--TVRIVTLKSALVSQFRKQF QFYKVREVNDY
984


WP_003739838
914
AD KATFIHRQLVETRQITKNVANILHQRFNNETDNHGNNME--QVRIVMLKSALVSQFRKQF QLYKVREVNDY
984


WP_014601172
914
AD KARFIHRQLVETRQITKNVANILHQRFNNETDNHGNTME--QVRIVTLKSALVSQFRKQF QLYKVREVNDY
984


WP_023548323
914
AD KARFIHRQLVETRQITKNVANILHQRFNYKTDDNEDTME--PVRIVTLKSALVSQFRKQF QLYKVREVNDY
984


WP_031665337
914
AD KARFIHRQLVETRQITKNVANILHQRFNKETDNHGNTME--QVRIVTLKSALVSQFRKQF QLYKVREVNDY
984


WP_031669209
914
AD KARFIHRQLVETRQITKNVANILHQRFNYKTDGNKDTME--TVRIVTLKSALVSQFRKQF QFYKVREVNDY
984


WP_033920898
914
AD KARFIHRQLVETRQITKNVANILHQRFNYKTDDNEDTME--PVRIVTLKSALVSQFRKQF QLYKVREVNDY
984


AKI42028
917
AD KARFIHRQLVETRQITKNVANILHQRFNNETDNHGNTME--QVRIVTLKSALVSQFRKQF QLYKVREVNDY
987


AKI50529
917
AD KARFIHRQLVETRQITKNVANILHQRFNYKTDDNEDTME--PVRIVTLKSALVSQFRKQF QLYKVREVNDY
987


EFR83390
362
AD KARFIHRQLVETRQITKNVANILHQRFNNETDNHGNTME--QVRIVTLKSALVSQFRKQF QLYKVREVNDY
432


WP_046323366
914
AD KARFIHRQLVETRQITKNVANILHQRFNCKKDESGNVIE--QVRIVTLKAALVSQFRKQF QLYKVREVNDY
984


AKE81011
927
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDFRKDF QFYKVREINNY
997


CUO82355
921
RD EERFINRQLVETRQITKNVTQIIEDHYST-------------TKVAAIRANLSHEFRVKN HIYKNRDINDY
980


WP_033162887
923
KD KERFINRQLVETRQIIKNVAVIINDHYTN-------------TNIVTVRAELSHQFRERY KIYKNRDINDF
982


AGZ01981
944
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDFRKDF QFYKVREINNY
1014


AKA60242
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDFRKDF QFYKVREINNY
981


AKS40380
911
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDFRKDF QFYKVREINNY
981


4UN5_B
915
LD KAGFIKRQLVETRQITKHVAQILDSRMNTKYDENDKLIR--EVKVITLKSKLVSDFRKDF QFYKVREINNY
985


WP_010922251
982

custom character

1051


WP_039695303
992
HHAHDAYLNAVVGTALLKKYPKL-ASEFVYGEYKKYDI S---SD------ KATAK--YfFYSNLM-NFFKTKVK
1058


WP_045635197
984
HHAHDAYLNAVVAKAILKKYPKL-EPEFVYGEYQKYDL SkdpKEV---EK ATEKY--F-FYSNLL-NFFKEEVH
1055


5AXW_A
703
HHAEDALI--------------IaNADFIFKEWKKLDK Nq-mFE----EK ETEQEykEiFITPHQiKHIKDFKD
771


WP_009880683
666
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDI S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
735


WP_010922251
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_011054416
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_011284745
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_011285506
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_011527619
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_012560673
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDI S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_014407541
981
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1050


WP_020905136
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_023080005
981
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1050


WP_023610282
981
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1050


WP_030125963
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_030126706
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_031488318
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_032460140
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDI S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_032461047
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDI S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_032462016
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_032462936
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_032464890
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_033888930
807
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
876


WP_038431314
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_038432938
981
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1050


WP_038434062
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


BAQ51233
893
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
962


KGE60162
157
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
226


KGE60856

-------------------------------------- ------------ ------------------------



WP_002989955
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_003030002
981
HHAHDAYLNAVVGNALLLKYPQL-EPEFVYGEYPKYN- S---YR---sRK SATEK--F1FYSNIL-RFFKKE--
1041


WP_003065552
992
HHAHDAYLNAVVGTALLKKYPKL-ASEFVYGEYKKYDI S---SD------ KATAK--YfFYSNLM-NFFKRVIR
1058


WP_001040076
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040078
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGLYRRKK- L---SKI---VR ATRKM--F-FYSNLM-NMFKRVVR
1057


WP_001040080
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040081
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040083
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040085
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040087
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040088
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040089
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040090
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040091
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040092
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040094
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040095
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040096
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040097
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040098
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040099
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040100
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040104
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040105
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040106
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040107
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040108
987
HHAHDAYLNAVVAKAILTKYPQL-EREFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040109
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_001040110
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_015058523
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_017643650
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_017647151
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_017648376
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_017649527
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_017771611
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_017771984
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


CFQ25032
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


CFV16040
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


KLJ37842
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


KLJ72361
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


KLL20707
1001
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1063


KLL42645
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_047207273
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_047209694
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_050198062
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_050201642
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_050204027
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_050881965
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_050886065
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


AHN30376
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


EA078426
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


CCW42055
987
HHAHDAYLNAVVAKAILTKYPQL-EPEFVYGDYPKYN- S---YKT---RK ATEKL--F-FYSNIM-NFFKTKVT
1049


WP_003041502
981
HHAHDAYLNAVIGTALLKKYPKL-ASEFVYGEFKKYDV S---DK---eIG KATAK--YfFYSNLM-NFFKKEVK
1050


WP_037593752
982
HHAHDAYLNAVVGNALLLKYPQL-EPEFVYGEYPKYN- S---YR---sRK SATEK--F1FYSNIL-RFFKKE--
1042


WP_049516684
982
HHAHDAYLNAVVGNALLLKYPQL-EPEFVYGEYPKYN- S---YR---sRK SATEK--F1FYSNIL-RFFKKE--
1042


GAD46167
981
HHAHDAYLNAVVGNALLLKYPQL-EPEFVYGEYPKYN- S---YR---sRK SATEK--F1FYSNIL-RFFKKE--
1041


WP_018363470
990
HHAHDAYLNAVVGTALLKKYPKL-APEFVYGEYKKYDV S---SDDhseMG KATAK--YfFYSNLM-NFFKRVIR
1062


WP_003043819
991
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKR--F-FYSNIM-NFFKTEVK
1060


WP_006269658
981
HHAHDAYLNAVVGNALLLKYPQL-EPEFVYGEYPKYN- S---YR---sRK SATEK--F1FYSNIL-RFFKKE--
1041


WP_048800889
981
HHAHDAYLNAVVGTALLKKYPKL-TSEFVYGEYKKYDV S---DND--eIG KATAK--YfFYSNLM-NFFKTEVK
1051


WP_012767106
981
HHAHDAYLNAVVGTALIKKYTKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKR--F-FYSNIM-NFFKTEIT
1050


WP_014612333
981
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKR--F-FYSNIM-NFFKTEIT
1050


WP_015017095
981
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKR--F-FYSNIM-NFFKTEIT
1050


WP_015057649
981
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKR--F-FYSNIM-NFFKTEIT
1050


WP_048327215
981
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKR--F-FYSNIM-NFFKTEIT
1050


WP_049519324
981
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKR--F-FYSNIM-NFFKTEIT
1050


WP_012515931
981
HHAHDAYLNAVVAKAILGKYPQL-APEFVYGDYPKYN- S---FKEr--QK ATQKM--L-FYSNIL-KFFKDQES
1043


WP_021320964
981
HHAHDAYLNAVVAKAILGKYPQL-APEFVYGDYPKYN- S---FKEr--QK ATQKT--L-FYSNIL-KFFKDQES
1043


WP_037581760
981
HHAHDAYLNAVVAKAILGKYPQL-APEFVYGDYPKYN- S---FKEr--QK ATQKT--L-FYSNIL-KFFKDQES
1043


WP_004232481
989
HHAHDAYLNAVVGTALLKKYPKL-APEFVYGEYKKYDV S---SDNhseLG KATAK--YfFYSNLM-NFFKTEVK
1061


WP_009854540
990
HHAHDAYLNAVVGTALLKKYPKL-ASEFVYGEYKKYDI S---SD------ KATAK--YfFYSNLM-NFFKTKVK
1056


WP_012962174
990
HHAHDAYLNAVVGTALLKKYPKL-APEFVYGEYKKYDI S---GD------ KATAK--YfFYSNLM-NFFKRVIR
1056


WP_039695303
992
HHAHDAYLNAVVGTALLKKYPKL-ASEFVYGEYKKYDI S---SD------ KATAK--YfFYSNLM-NFFKTKVK
1058


WP_014334983
989
HHAHDAYLNAVVGTALLKKYPKL-TPEFVYGEYKKYDV S---SDDyseMG KATAK--YfFYSNLM-NFFKTEVK
1061


WP_003099269
982
HHAQDAYLNAVVGTALLKKYPKL-EAEFVYGDYKHYDL P---DSS1--GK ATTRM--F-FYSNLM-NFFKKEIK
1051


AHY15608
982
HHAQDAYLNAVVGTALLKKYPKL-EAEFVYGDYKHYDL P---DSS1--GK ATTRM--F-FYSNLM-NFFKKEIK
1051


AHY17476
982
HHAQDAYLNAVVGTALLKKYPKL-EAEFVYGDYKHYDL P---DSS1--GK ATTRM--F-FYSNLM-NFFKKEIK
1051


ESR09100

-------------------------------------- ------------ ------------------------



AGM98575
982
HHAQDAYLNAVVGTALLKKYPKL-EAEFVYGDYKHYDL P---DSS1--GK ATTRM--F-FYSNLM-NFFKKEIK
1051


ALF27331
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_018372492
995
HHAHDAYLNAVVAQALLKVYPKF-ERELVYGSYVKESI ----FS----RK ATERM---rMYNNIL-KFISKD--
1055


WP_045618028
985
HHAHDPYLNAVVAKAILKKYPKL-EPEFVYGDYQKYDL TkdpKEV---EK ATEKY--F-FYSNLL-NFFKEEVH
1056


WP_045635197
984
HHAHDAYLNAVVAKAILKKYPKL-EPEFVYGEYQKYDL SkdpKEV---EK ATEKY--F-FYSNLL-NFFKEEVH
1055


WP_002263549
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002263887
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002264920
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002269043
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002269448
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002271977
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002272766
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HE---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002273241
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002275430
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HE---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002276448
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002277050
984
HHAHDAYLNAVVVKALLVKYPKL-EPEFVYGEYPKYN- S---YR---eRK ATQKM--F-FYSNIM-NMFKSKVK
1046


WP_002277364
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002279025
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HE---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002279859
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002280230
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002281696
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002282247
984
HHAHDAYLNAVVVKALLVKYPKL-EPEFVYGEYPKYN- S---YR---eRK ATQKM--F-FYSNIM-NMFKSKVK
1046


WP_002282906
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002283846
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002287255
982
HHTHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002288990
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002289641
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002290427
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002295753
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002296423
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002304487
996
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKG--
1055


WP_002305844
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002307203
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002310390
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_002352408
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_012997688
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_014677909
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_019312892
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_019313659
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_019314093
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_019315370
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HE---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_019803776
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_019805234
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_024783594
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_024784288
984
HHAHDAYLNAVVVKALLVKYPKL-EPEFVYGEYLKYN- S---YR---eRK ATQKM--F-FYSNIM-NMFKSKVK
1046


WP_024784666
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_024784894
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_024786433
984
HHAHDAYLNAVVVKALLVKYPKL-EPEFVYGEYPKYN- S---YR---eRK ATQKM--F-FYSNIM-NMFKSKVK
1046


WP_049473442
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HE---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


WP_049474547
982
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1041


EMC03581
975
HHAHDAYLNAVIGKALLGVYPQL-EPEFVYGDYPHFH- G---HK---eNK ATAKK--F-FYSNIM-NFFKKD--
1034


WP_000428612
987
HHAHDAYLNAVVAKAILKKYPKL-EPEFVYGDYQKYDL SkdpKEI---EK ATEKY--F-FYSNLL-NFFKEEVH
1058


WP_000428613
985
HHAHDAYLNAVVAKAILKKYPKL-EPEFVYGDYQKYDL SrnpKEV---EK ATEKY--F-FYSNLL-NFFKEEVH
1056


WP_049523028
980
HHAHDAYLNAVVAKAILKKYPKL-EPEFVYGDYQKYDL TkdpKEI---EK ATEKY--F-FYSNLL-NFFKDKVY
1051


WP_003107102
951
HHAHDAYLNAVVGTALLKKYPKL-EAEFVYGDYKHYDL S---DTS1--GK ATAKM--F-FYSNIM-NFFKKEVR
1020


WP_054279288
983
HHAHDAYLNAVVGTALLKMYPKL-ASEFVYGDYQKYDL S---GKAs--GH ATAKY--F-FYSNLM-NFFKSEVK
1052


WP_049531101
985
HHAHDAYLNAVVAKAILKKYPKL-EPEFVYGDYQKYDL SrdpKEI---EK ATEKY--F-FYSNLL-NFFKEEVH
1056


WP_049538452
985
HHAHDAYLNAVVAKAILKKYPKL-EPEFVYGDYQKYDL SkdpKDI---EK ATEKY--F-FYSNLL-NFFKEEVH
1056


WP_049549711
987
HHAHDAYLNAVVAKAILKKYPKL-EPEFVYGDYQKNDL SkdpKDI---EK ATEKY--F-FYSNLL-NFFKEEVH
1058


WP_007896501
988
HHAHDAYLNAVVGTALLKKYPKL-EAEFVYGDYKHFDL S---DPS1--GK ATAKV--F-FYSNIM-NFFKEELS
1057


EFR44625
940
HHAHDAYLNAVVGTALLKKYPKL-EAEFVYGDYKHFDL S---DPS1--GK ATAKV--F-FYSNIM-NFFKEELS
1009


WP_002897477
984
HHAHDAYLNAVVAKAILKKYPKL-EPEFVYGDYQKYDL FkpsKEI---EK ATEKY--F-FYSNLL-NFFKEEVL
1055


WP_002906454
984
HHAHDAYLNAVVAKAILKKYPKL-EPEFVYGDYQKYDL SkasNTI---DK ATEKY--F-FYSNLL-NFFKEKVR
1055


WP_009729476
985
HHAHDAYLNAVVAKAILKKYPKL-EPEFVYGDYQKYDL SkdpKEI---EK ATEKY--F-FYSNLL-NFFKEEVH
1056


CQR24647
984
HHAHDAYLNAVVAKALLIRYPKL-EPEFVYGEYPKYN- S---YRE---RK ATEKM--F-FYSNIM-NMFKTTIK
1046


WP_000066813
989
HHAHDAYLNAVLAKAILKKYPKL-EPEFVYGDYQKYDL SrepKEV---EK ATQKY--F-FYSNLL-NFFKEEVH
1060


WP_009754323
985
HHAHDAYLNAVVAKAILKKYPKL-EPEFVYGDYQKYDL SkdpKEV---EK ATEKY--F-FYSNLL-NFFKEEVH
1056


WP_044674937
986
HHAHDAYLNAVVATALLKKYPQL-APEFVYGDYPKYN- S---YKS---RK ATEKV--L-FYSNIM-NFFRRVLV
1048


WP_044676715
988
HHAHDAYLNAVVATALLKKYPQL-APEFVYGDYPKYN- S---YKS---RK ATEKV--L-FYSNIM-NFFRRVLV
1050


WP_044680361
988
HHAHDAYLNAVVATALLKKYPQL-APEFVYGDYPKYN- S---YKS---RK ATEKV--L-FYSNIM-NFFRRVLV
1050


WP_044681799
986
HHAHDAYLNAVVATALLKKYPQL-APEFVYGDYPKYN- S---YKS---RK ATEKV--L-FYSNIM-NFFRRVLV
1048


WP_049533112
981
HHAHDAYLNAVIGTALLKKYPKL-ASEFVYGEFKKYDV S---DK---eIG KATAK--YfFYSNLM-NFFKKEVK
1050


WP_029090905
952
HHAQDAFLVAFLGTNITSNYPKI-EMEYLFKGYQHYLN ------Ev--GK AAKPKftF-IVENLS---------
1007


WP_006506696
977
HHAHDAYIVALIGGFMRDRYPNMhDSKAVYSEYMKMFR ----NKNd--QK -----g---FVINSM-NYPY-EV-
1038


AIT42264
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_034440723
981
HHAHDAYLNGVIALKLLELYPYM-AKDLIYGKYSYHRK G---------DK ATQAK--Y-KMSNII-ERFSQDL-
1041


AKQ21048
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


WP_004636532
981
HHGHDAYLNAVVATTIMKVYPNL-KPQFVYGQYKKTSM ----FKE---EK ATARK--H-FYSNIT-KFFKKEKV
1042


WP_002364836
988
HHGQDAYLNCVVATTLLKVYPNL-APEFVYGEYPKFQT ----FKE---NK ATAKA--I-IYTNLL-RFFTED--
1047


WP_016631044
939
HHGQDAYLNCVVATTLLKVYPNL-APEFVYGEYPKFQT ----FKE---NK ATAKA--I-IYTNLL-RFFTED--
998


EMS75795
723
HHAHDAYLNGVVAIALLKKYPKL-EPEFVYGNYTKFNL ----AT---eNK ATAKK--E-FYSNIL-RFFEKE--
782


WP_002373311
988
HHGQDAYLNCVVATTLLKVYPNL-APEFVYGEYPKFQA ----FKE---NK ATAKT--I-IYTNLM-RFFTED--
1047


WP_002378009
988
HHGQDAYLNCVVATTLLKVYPNL-APEFVYGEYPKFQT ----FKE---NK ATAKA--I-IYTNLL-RFFTED--
1047


WP_002407324
988
HHGQDAYLNCVVATTLLKVYPNL-APEFVYGEYPKFQT ----FKE---NK ATAKA--I-IYTNLL-RFFTED--
1047


WP_002413717
988
HHGQDAYLNCVVATTLLKVYPNL-APEFVYGEYPKFQT ----FKE---NK ATAKA--I-IYTNLL-RFFTED--
1047


WP_010775580
990
HHGQDAYLNCVVATTLLKVYPNL-APEFVYGEYPKFQA ----FKE---NK ATAKA--I-IYTNLL-RFFTED--
1049


WP_010818269
988
HHGQDAYLNCVVATTLLKVYPNL-APEFVYGEYPKFQT ----FKE---NK ATAKA--I-IYTNLL-RFFTED--
1047


WP_010824395
988
HHGQDAYLNCVVATTLLKVYPNL-APEFVYGEYPKFQT ----FKE---NK ATAKT--I-IYTNLM-RFFTED--
1047


WP_016622645
988
HHGQDAYLNCVVATTLLKVYPNL-APEFVYGEYPKFQT ----FKE---NK ATAKA--I-IYTNLL-RFFTED--
1047


WP_033624816
988
HHGQDAYLNCVVATTLLKVYPNL-APEFVYGEYPKFQA ----FKE---NK AMAKA--I-IYTNLL-RFFTED--
1047


WP_033625576
988
HHGQDAYLNCVVATTLLKVYPNL-APEFVYGEYPKFQA ----FKE---NK ATAKA--I-IYTNLM-RFFTEV--
1047


WP_033789179
988
HHGQDAYLNCVVATTLLKVYPNL-APEFVYGEYPKFQA ----FKE---NK ATAKA--I-IYTNLL-RFFTED--
1047


WP_002310644
989
HHAHDAYLNGVVALALLKKYPQL-APEFVYGEYLKFNA ----HK---aNK ATVKK--E-FYSNIM-KFFESD--
1048


WP_002312694
990
HHAHDAYLNGVVALALLKKYPQL-APEFVYGEYLKFNA ----HK---aNK ATVKK--E-FYSNIM-KFFESD--
1049


WP_002314015
990
HHAHDAYLNGVVALALLKKYPQL-APEFVYGEYLKFNA ----HK---aNK ATVKK--E-FYSNIM-KFFESD--
1049


WP_002320716
990
HHAHDAYLNGVVALALLKKYPQL-APEFVYGEYLKFNA ----HK---aNK ATVKK--E-FYSNIM-KFFESD--
1049


WP_002330729
989
HHAHDAYLNGVVALALLKKYPQL-APEFVYGEYLKFNA ----HK---aNK ATVKK--E-FYSNIM-KFFESD--
1048


WP_002335161
990
HHAHDAYLNGVVALALLKKYPQL-APEFVYGEYLKFNA ----HK---aNK ATVKK--E-FYSNIM-KFFESD--
1049


WP_002345439
990
HHAHDAYLNGVVALALLKKYPQL-APEFVYGEYLKFNA ----HK---aNK ATVKK--E-FYSNIM-KFFESD--
1049


WP_034867970
980
HHAHDAYLNGFIANVLLKRYPKL-APEFVYGKYVKYSL ----AR---eNK ATAKK--E-FYSNIL-KFLESD--
1039


WP_047937432
990
HHAHDAYLNGVIALALLKKYPQL-APEFVYGEYLKFNA ----HK---aNK ATVKK--E-FYSNIM-KFFESD--
1049


WP_010720994
980
HHAHDAYLNGFIANVLLKRYPKL-APEFVYGKYVKYSL ----AR---eNK ATAKK--E-FYSNIL-KFLESD--
1039


WP_010737004
980
HHAHDAYLNGFIANVLLKRYPKL-APEFVYGKYVKYSL ----AR---eNK ATAKK--E-FYSNIL-KFLESD--
1039


WP_034700478
980
HHAHDAYLNGFIANVLLKRYPKL-APEFVYGKYVKYSL ----AR---eNK ATAKK--E-FYSNIL-KFLESD--
1039


WP_007209003
978
HHAHDAYLNAVVALSLLRVYPQL-KPEFVYGEYGKNS- ----IHDq--NK ATIKK---qFYSNIT-RYFASK--
1037


WP_023519017
974
HHAHDAYLNGVVAMTLLKKYPKL-APEFVYGSYIKGDI ----NQ---iNK ATAKK--E-FYSNIM-KFFESE--
1033


WP_010770040
986
HHGHDAYLNGVVANSLLRVYPQL-QPEFVYGDYPKFNA ----YKA---NK ATAKK--Q-LYTNIM-KFFAED--
1045


WP_048604708
983
HHAHDAYLNGVVATALLKIYPQL-EPEFVYGEFHRFNA ----FKE---NK ATAKK--Q-FYSNLM-EFSKSD--
1042


WP_010750235
983
HHAHDAYLNAVVALALLKKYPRL-APEFVYGSFAKFHL ----VK---eNK ATAKK--E-FYSNIL-KFFEKE--
1042


AII16583
1021
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1090


WP_029073316
988
HHAHDAYIATILGTYIGHRFESL-DAKYIYGEYQKIFR ----NKNk--DK ---KDg---FILNSM-RNLYADK-
1052


WP_031589969
988
HHAHDAYIATILGTYIGHRFESL-DAKYIYGEYKRIFR ----QKNk--GK ---NDg---FILNSM-RNIYADK-
1052


KDA45870
973
HHAHDAYLNAVVANLIMAKYPEL-EPEFVYGKYRKTK- ----FKG1--GK ATAKN---tLYANVL-YFLKENEV
1034


WP_039099354
991
HHAFDAYLTAFVGLYLLKRYPKL-KPYFVYGEYQKAS- ----QQ----DK ---RN--F----NFL-NGLKKD--
1043


AKP02966
1000
HHAQDAYLASFLGTYRLRRFPTD-EMLLMNGEYNKFYG -----KElysKK -SRKN-gF-IISPLV---------
1062


WP_010991369
985
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGDYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-LFFAQK--
1044


WP_033838504
985
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGDYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-LFFAQK--
1044


EHN60060
988
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGDYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-LFFAQK--
1047


EFR89594
754
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGDYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-LFFAQK--
813


WP_038409211
985
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGDYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-RFFAKE--
1044


EFR95520
604
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGDYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-RFFAKE--
663


WP_003723650
985
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGEYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-LFFAQK--
1044


WP_003727705
985
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGEYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-LFFAQK--
1044


WP_003730785
985
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGEYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-LFFAQK--
1044


WP_003733029
985
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGEYHQFGW ----FKA---NK ATAKK--Q-FYTNIM-LFFAQK--
1044


WP_003739838
985
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGEYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-LFFAQK--
1044


WP_014601172
985
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGEYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-LFFGQK--
1044


WP_023548323
985
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGEYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-LFFAQK--
1044


WP_031665337
985
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGEYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-LFFAQK--
1044


WP_031669209
985
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGEYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-LFFAQK--
1044


WP_033920898
985
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGEYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-LFFAQK--
1044


AKI42028
988
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGEYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-LFFGQK--
1047


AKI50529
988
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGEYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-LFFAQK--
1047


EFR83390
433
HHAHDAYLNGVVANTLLKVYPQL-EPEFVYGEYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-LFFAQK--
492


WP_046323366
985
HHAHDAYLNCVVANTLLKVYPQL-EPEFVYGDYHQFDW ----FKA---NK ATAKK--Q-FYTNIM-LFFAKK--
1044


AKE81011
998
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1067


CUO82355
981
HHAHDAYIVALIGGFMRDRYPNMhDSKAVYSEYMKMFR ----NKNd--QK -----g---FVINSM-NYPY-EV-
1042


WP_033162887
983
HHAHDAYIACIVGQFMHQNFEHL-DAKIIYGQYK---- -----KNy--KK ---NYg---FILNSM-NHLQSDI-
1042


AGZ01981
1015
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1084


AKA60242
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


AK540380
982
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1051


4UN5_B
986
HHAHDAYLNAVVGTALIKKYPKL-ESEFVYGDYKVYDV S---EQEi--GK ATAKY--F-FYSNIM-NFFKTEIT
1055


WP_010922251
1052

custom character  GGFSK ESIL-PKR-

1114


WP_039695303
1059
YAD-GTVFERPIIE T-NAD-GE-IAWNKQIDFEKVRKVLS-YPQVNIVKKVETQT GGFSK ESIL-PKG-
1120


WP_045635197
1056
YAD-GTIVKRENIE Y-SKDLGE-IAWNKEKDFAIIKKVLS-LPQVNIVKKREVQT GGFSK ESIL-PKG-
1118


5AXW_A
772
YKYsHRVDKKPNRE VNNLN-GL---YDKDND--KLKKLINkSPEKLLMYHHDPQT --YQK KLIMeQYGd
852


WP_009880683
736
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
798


WP_010922251
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_011054416
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_011284745
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_011285506
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_011527619
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_012560673
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_014407541
1051
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1113


WP_020905136
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_023080005
1051
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1113


WP_023610282
1051
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1113


WP_030125963
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_030126706
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_031488318
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_032460140
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_032461047
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_032462016
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_032462936
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_032464890
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_033888930
877
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
939


WP_038431314
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_038432938
1051
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1113


WP_038434062
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


BAQ51233
963
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1025


KGE60162
227
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
289


KGE60856
1
------------IE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
52


WP_002989955
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_003030002
1042
-----------DIQ T-NED-GE-IAWNKEKHIKILRKVLS-YPQVNIVKKTEEQT GGFSK ESIL-PKG-
1093


WP_003065552
1059
YSN-GKVIVRPVVE Y-SKD-TEdIAWDKKSNERTICKVLS-YPQVNIVKKVETQT GGFSK ESIL-PKG-
1121


WP_001040076
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040078
1058
LAD-GSIVVRPVIE TGRYM-GK-TAWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1120


WP_001040080
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040081
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040083
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040085
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040087
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040088
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040089
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040090
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040091
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040092
1050
LAD-ETVVVKDDIE VNNET-GE-IAWDKKKHFATVRKVLS-YPQVNIVKKTEVQT GGFSK ESIL-AHS-
1112


WP_001040094
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040095
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEVQT GGFSK ESIL-AHG-
1112


WP_001040096
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEVQT GGFSK ESIL-AHG-
1112


WP_001040097
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040098
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040099
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040100
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040104
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040105
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040106
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040107
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040108
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040109
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_001040110
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_015058523
1050
LAD-ETVVVKDDIE VNNET-GE-IAWDKKKHFATVRKVLS-YPQVNIVKKTEVQT GGFSK ESIL-AHS-
1112


WP_017643650
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_017647151
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_017648376
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_017649527
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_017771611
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_017771984
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


CFQ25032
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


CFV16040
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


KLJ37842
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


KLJ72361
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


KLL20707
1064
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1126


KLL42645
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_047207273
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_047209694
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_050198062
1050
LAD-GTVVIKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_050201642
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_050204027
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQVNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_050881965
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_050886065
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


AHN30376
1050
LAD-ETVVVKDDIE VNNET-GE-IAWDKKKHFATVRKVLS-YPQVNIVKKTEVQT GGFSK ESIL-AHS-
1112


EA078426
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


CCW42055
1050
LAD-GTVVVKDDIE VNNDT-GE-IVWDKKKHFATVRKVLS-YPQNNIVKKTEIQT GGFSK ESIL-AHG-
1112


WP_003041502
1051
FAD-GTVVERPDIE T-SED-GE-IAWNKQTDFKIVRKVLS-YPQVNIVKKTEVQT HGLDR PSPK-PKP-
1122


WP_037593752
1043
-----------DIQ T-NED-GE-IAWNKEKHIKILRKVLS-YPQVNIVKKTEEQT GGFSK ESIL-PKG-
1094


WP_049516684
1043
-----------DIQ T-NED-GE-IAWNKEKHIKILRKVLS-YPQVNIVKKTEEQT GGFSK ESIL-PKG-
1094


GAD46167
1042
-----------DIQ T-NED-GE-IAWNKEKHIKILRKVLS-YPQVNIVKKTEEQT GGFSK ESIL-PKG-
1093


WP_018363470
1063
YSN-GKVIVRPVVE Y-SKDtGE-IAWNKRTDFEKVRKVLS-YPQVNIVKKVETQT GGFSK ESIL-PKG-
1125


WP_003043819
1061
LAN-GEIRKRPLIE TNGET-GE-VVWNKEKDFATVRKVLA-MPQVNIVKKTEVQT GGFSK ESIL-SKR-
1123


WP_006269658
1042
-----------DIQ T-NED-GE-IAWNKEKHIKILRKVLS-YPQVNIVKKTEEQT GGFSK ESIL-PKG-
1093


WP_048800889
1052
FAD-GTVVERPDIE T-SED-GE-IAWNKQTDFKIVRKVLS-YPQVNIVKKVEKQT GRFSK ESIL-PKG-
1113


WP_012767106
1051
LAN-GEIRKRPLIE TNEET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GALTN ESIY-ARG-
1113


WP_014612333
1051
LAN-GEIRKRPLIE TNEET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GALTN ESIY-ARG-
1113


WP_015017095
1051
LAN-GEIRKRPLIE TNEET-GE-IVWNKGRDFATVRKVLS-MPQVNIVKKTEVQT GALTN ESIY-ARG-
1113


WP_015057649
1051
LAN-GEIRKRPLIE TNEET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GALTN ESIY-ARG-
1113


WP_048327215
1051
LAN-GEIRKRPLIE TNEET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GALTN ESIY-ARG-
1113


WP_049519324
1051
LAN-GEIRKRPLIE TNEET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GALTN ESIY-ARG-
1113


WP_012515931
1044
L------------H VNSD--GE-EIWNANKHLPIIKNVLS-IPQVNIVKKTEVQT GGFYK ESIL-SKG-
1094


WP_021320964
1044
L------------H VNSD--GE-EIWNANKHLPIIKNVLS-IPQVNIVKKTEVQT GGFYK ESIL-SKG-
1094


WP_037581760
1044
L------------H VNSD--GE-EIWNANKHLPIIKNVLS-IPQVNIVKKTEVQT GGFYK ESIL-SKG-
1094


WP_004232481
1062
YAD-GRVFERPDIE T-NAD-GE-VVWNKQRDFNIVRKVLS-YPQVNIVKKVEVQT GGFSK ESIL-PKG-
1123


WP_009854540
1057
YAD-GTVFERPIIE T-NAD-GE-IAWNKQIDFEKVRKVLS-YPQVNIVKKVETQT GGFSK ESIL-PKG-
1118


WP_012962174
1057
YSN-GKVVVRPVIE C-SKDtGE-IAWNKQTDFEKVRRVLS-YPQVNIVKKVETQT GGFSK ESIL-PKG-
1119


WP_039695303
1059
YAD-GTVFERPIIE T-NAD-GE-IAWNKQIDFEKVRKVLS-YPQVNIVKKVETQT GGFSK ESIL-PKG-
1120


WP_014334983
1062
YAD-GRVFERPDIE T-NAD-GE-VVWNKQKDFDIVRKVLS-YPQVNIVKKVEAQT GGFSK ESIL-SKG-
1123


WP_003099269
1052
LAD-DTIFTRPQIE VNTET-GE-IVWDKVKDMQTIRKVMS-YPQVNIVMKTEVQT GGFSK ESIW-PKG-
1114


AHY15608
1052
LAD-DTIFTRPQIE VNTET-GE-IVWDKVKDMQTIRKVMS-YPQVNIVMKTEVQT GGFSK ESIW-PKG-
1114


AHY17476
1052
LAD-DTIFTRPQIE VNTET-GE-IVWDKVKDMQTIRKVMS-YPQVNIVMKTEVQT GGFSK ESIW-PKG-
1114


ESR09100

-------------- ----------------------------------------- ----- ---------



AGM98575
1052
LAD-DTIFTRPQIE VNTET-GE-IVWDKVKDMQTIRKVMS-YPQVNIVMKTEVQT GGFSK ESIW-PKG-
1114


ALF27331
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_018372492
1056
--K----------K --DQEtGE-IVWDKKEIENIVKKVIY-SSPVNIVKKREEQS GALFK QSNM-AVGy
1108


WP_045618028
1057
YAD-GTIVKRENIE Y-SKDtGE-IAWNKEKDFATIKKVLS-LPQVNIVKKTEEQT GGLFD NNIV-SKKk
1124


WP_045635197
1056
YAD-GTIVKRENIE Y-SKDtGE-IAWNKEKDFAIIKKVLS-LPQVNIVKKREVQT GGFSK ESIL-PKG-
1118


WP_002263549
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002263887
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002264920
1042
-----------DVR T-DKN-GE-IIWKKDEYISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002269043
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002269448
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002271977
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002272766
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002273241
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002275430
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002276448
1042
-----------DVR T-DRN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002277050
1047
LAD-DQIVERPMIE VNDET-GE-IAWDKTKHITTVKKVLS-YPQVNIVKKVEEQT GGLFD -----PKS-
1111


WP_002277364
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002279025
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002279859
1042
-----------DVR T-DKN-GE-IIWKKDEYISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002280230
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002281696
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002282247
1047
LAD-DQIVERPMIE VNDET-GE-IAWDKTKHITTVKKVLS-YPQVNIVKKVEEQT GGLFD -----PKS-
1111


WP_002282906
1042
-----------DVR I-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002283846
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002287255
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002288990
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002289641
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002290427
1042
-----------DVR T-DKN-GE-IIWKKDEYISNIKKVLS-YPQVNIVKKVEEQT GGFFK ESIL-PKG-
1093


WP_002295753
1042
-----------DVR T-DKN-GE-IIWKKDEYISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002296423
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002304487
1056
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1107


WP_002305844
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002307203
1042
-----------DVR T-DKN-GE-IIWKKDEYISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_002310390
1042
-----------DVR T-DKN-GE-IIWKKDEYISNIKKVLS-YPQVNIVKKVEEQT GGFFK ESIL-PKG-
1093


WP_002352408
1042
-----------DVR T-DKN-GE-IIWKKDEYISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_012997688
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_014677909
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_019312892
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_019313659
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_019314093
1042
-----------DVR T-DKN-GE-IIWKKDEYISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_019315370
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_019803776
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_019805234
1042
-----------DVR T-DKN-GE-IIWKKDEYISNIKKVLS-YPQVNIVKKVEEQT GGFFK ESIL-PKG-
1093


WP_024783594
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_024784288
1047
LAD-DQIVERPMIE VNDET-GE-IAWDKTKHITTVKKVLS-YPQVNIVKKVEEQT GGLFD -----PKS-
1111


WP_024784666
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_024784894
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_024786433
1047
LAD-DQIVERPMIE VNDET-GE-IAWDKTKHITTVKKVLS-YPQVNIVKKVEEQT GGLFD -----PKS-
1111


WP_049473442
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


WP_049474547
1042
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1093


EMC03581
1035
-----------DVR T-DKN-GE-IIWKKDEHISNIKKVLS-YPQVNIVKKVEEQT GGFSK ESIL-PKG-
1086


WP_000428612
1059
YAD-GTIVKRENIE Y-SKDtGE-IAWNKEKDFATIKKVLS-LPQVNIVKKREVQT GGFSK ESIL-PKG-
1121


WP_000428613
1057
YAD-GTIVKRENIE Y-SKDtGE-IAWNKEKDFATIKKVLS-YPQVNIVKKREVQT GGFSK ESIL-PKG-
1119


WP_049523028
1052
YAD-GTIIQRGNVE Y-SKDtGE-IAWNKKRDFAIVRKVLS-YPQVNIVKKTEEQT GGFSK ESIL-PKG-
1114


WP_003107102
1021
LAD-GTVITRPQIE TNTET-GE-IVWDKVKDIKTIRKVLS-IPQINVVKKTEVQT GGFSK ESIL-SKR-
1083


WP_054279288
1053
LAN-GNIIKRSPIE VNEET-GE-IVWDKTKDFGTVRKVLS-APQVNIVKKTEIQT GGFSN ETIL-SKG-
1115


WP_049531101
1057
YAD-GTIVKRENIE Y-SKDtGE-IAWNKEIDFATIRKILS-LSQVNIVKKTEEQT GGLFD NNIV-SKKk
1124


WP_049538452
1057
YAD-GTIVKRENIE Y-SKDtGE-IAWNKEKDFATIKKILS-LPQVNIVKKTEEQT GGLFD NNIV-SKKk
1124


WP_049549711
1059
YAD-GTIVKRENIE Y-SKDtGE-IAWNKEKDFATIKKVLS-YPQVNIVKKTEEQT GGLFD NNIV-SKEk
1126


WP_007896501
1058
LAD-GTLMKRPVIE TNTET-GE-VVWDKVKDFKTIRKVLS-YPQVNIVKKTEIQS GAFSK ESVL-SKG-
1120


EFR44625
1010
LAD-GTLMKRPVIE TNTET-GE-VVWDKVKDFKTIRKVLS-YPQVNIVKKTEIQS GAFSK ESVL-SKG-
1072


WP_002897477
1056
YAD-GTIRKRENIE Y-SKDtGE-IAWDKEKDFATIKKVLS-YPQVNIVKKREVQT GGFSK ESIL-PKG-
1118


WP_002906454
1056
YAD-GTIKKRENIE Y-SNDtGE-IAWNKEKDFATIKKVLS-LPQVNIVKKTEEQT GGLFD NNIV-SKKk
1123


WP_009729476
1057
YAD-GTIVKRENIE Y-SKDtGE-IAWNKEKDFATIKKVLS-LPQVNIVKKREVQT GGFSK ESIL-PKG-
1119


CQR24647
1047
LAD-GRVVEKPVIE ANEET-GE-IAWDKTKHFANVKKVLS-YPQVSIVKKVEEQT GGFSK ESIL-PKG-
1109


WP_000066813
1061
YAD-GTIVKRENIE Y-SKDtGE-IAWNKEKDFATVKKVLS-LPQVNIVKKTEVQT GGFSK ESIL-PKG-
1123


WP_009754323
1057
YAD-GTIVKRENIE Y-SKDtGE-IAWNKEKDFVTIKKVLS-YPQVNIVKKREVQT GGFSK ESIL-PKG-
1119


WP_044674937
1049
YSKtGEVRIRPVIE VNKET-GE-IVWDKKSDFRTVRKVLS-YPQVNVVKKVEMQT GGFSK ESIL-QHG-
1112


WP_044676715
1051
YSKtGEVRIRPVIE VNKET-GE-IVWDKKSDFRTVRKVLS-YPQVNVVKKVEMQT GGFSK ESIL-QHG-
1114


WP_044680361
1051
YSKtGEVRIRPVIE VNKET-GE-IVWDKKSDFRTVRKVLS-YPQVNVVKKVEMQT GGFSK ESIL-QHG-
1114


WP_044681799
1049
YSKtGEVRIRPVIE VNKET-GE-IVWDKKSDFKTVRKVLS-YPQVNVVKKVEMQT GGFSK ESIL-QHG-
1112


WP_049533112
1051
FAD-GTVVERPDIE T-SED-GE-IAWNKQTDFKIVRKVLS-YPQVNIVKKTEVQT HGLDR PSPK-PKP-
1122


WP_029090905
1008
-KQ----------Q --NSTtGE-VKWNPEVDIAKLKRILN-FKQCNIVRKVEEQS GALFK ETIY-PVEe
1061


WP_006506696
1039
--D----------- ------GK-LIWNP-DLINEIKKCFY-YKDCYCTTKLDQKS GQLFN -TVL-SNDa
1084


AIT42264
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_034440723
1042
------------LA --NPD-GE-IAWEKDKDLNTIRKVLS-SKQINIIKKAEEGK GRLFK ETIN-SRPs
1092


AKQ21048
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


WP_004636532
1043
-------------- VNEET-GE-ILWDTERHLSTIKRVLS-WKQMNIVKKVEKQK GQLWK ETIY-PKG-
1092


WP_002364836
1048
--E----------P RFTKD-GE-ILWSN-SYLKTIKKELN-YHQMNIVKKVEVQK GGFSK ESIK-PKG-
1098


WP_016631044
999
--E----------P RFTKD-GE-ILWSN-SYLKTIKKELN-YHQMNIVKKVEVQK GGFSK ESIK-PKG-
1049


EMS75795
783
--E----------Y SYDEN-GE-IFWDKARHIPQIKKVIS-SHQVNIVKKVEVQT GGFYK ETVN-PKG-
834


WP_002373311
1048
--E----------P RFTKD-SE-ILWSN-SYLKTIKKELN-YHQMNIVKKVEVQK GGFSK ESIK-PKG-
1098


WP_002378009
1048
--E----------P RFTKD-GE-ILWSN-SYLKTIKKELN-YHQMNIVKKVEVQK GGFSK ESIK-PKG-
1098


WP_002407324
1048
--E----------P RFTKD-GE-ILWSN-SYLKTIKKELN-YHQMNIVKKVEVQK GGFSK ESIK-PKG-
1098


WP_002413717
1048
--E----------P RFTKD-GE-ILWSN-SYLKTIKKELN-YHQMNIVKKVEVQK GGFSK ESIK-PKG-
1098


WP_010775580
1050
--E----------P RFTKD-GE-ILWSN-SYLKTIKKELN-YHQMNIVKKVEVQK GGFSK ESIK-PKG-
1100


WP_010818269
1048
--E----------P RFTKD-GE-ILWSN-SYLKTIKKELN-YHQMNIVKKVEVQK GGFSK ESIK-PKG-
1098


WP_010824395
1048
--E----------P RFTKD-GE-ILWSN-SYLKTIKKELN-YHQMNIVKKVEVQK GGFSK ESIK-PKG-
1098


WP_016622645
1048
--E----------P RFTKD-GE-ILWSN-SYLKTIKKELN-YHQMNIVKKVEVQK GGFSK ESIK-PKG-
1098


WP_033624816
1048
--E----------P RFTKD-GE-ILWSN-SYLKTIKKELN-YHQMNIVKKVEVQK GGFSK ESIK-PKG-
1098


WP_033625576
1048
--E----------P RFTKD-GE-ILWSN-SYLKTIKKELN-YHQMNIVKKVEVQK GGFSK ESIK-PKG-
1098


WP_033789179
1048
--E----------P RFTKD-GE-ILWSN-SYLKTIKKELN-YHQMNIVKKVEVQK GGFSK ESIK-PKG-
1098


WP_002310644
1049
--T----------P VCDEN-GE-IFWDKSKSIAQVKKVIN-HHHMNIVKKTEIQK GGFSK ETVE-PKK-
1100


WP_002312694
1050
--T----------P VCDEN-GE-IFWDKSKSIAQVKKVIN-HHHMNIVKKTEIQK GGFSK ETVE-PKK-
1101


WP_002314015
1050
--T----------P VCDEN-GE-IFWDKSKSIAQVKKVIN-HHHMNIVKKTEIQK GGFSK ETVE-PKK-
1101


WP_002320716
1050
--T----------P VCDEN-GE-IFWDKSKSIAQVKKVIN-HHHMNIVKKTEIQK GGFSK ETVE-PKK-
1101


WP_002330729
1049
--T----------P VCDEN-GE-IFWDKSKSIAQVKKVIN-HHHMNIVKKTEIQK GGFSE ETVE-PKK-
1100


WP_002335161
1050
--T----------P VCDEN-GE-IFWDKSKSIAQVKKVIN-HHHMNIVKKTEIQK GGFSK ETVE-PKK-
1101


WP_002345439
1050
--T----------P VCDEN-GE-IFWDKSKSIAQVKKVIN-HHHMNIVKKTEIQK GGFSK ETVE-PKK-
1101


WP_034867970
1040
--E----------P FCDEN-GE-IYWEKSHHLPRIKKVLS-SHQVNVVKKVEQQK GGFYK ETVN-SKE-
1091


WP_047937432
1050
--T----------P VCDEN-GE-IFWDKSKSIAQVKKVIN-HHHMNIVKKTEIQK GGFSK ETVE-PKK-
1101


WP_010720994
1040
--E----------P FCDEN-GE-IYWEKSHHLPRIKKVLS-SHQVNVVKKVEQQK GGFYK ETVN-SKE-
1091


WP_010737004
1040
--E----------P FCDEN-GE-IYWEKSHHLPRIKKVLS-SHQVNVVKKVEQQK GGFYK ETVN-SKE-
1091


WP_034700478
1040
--E----------P FCDEN-GE-IYWEKSHHLPRIKKVLS-SHQVNVVKKVEQQK GGFYK ETVN-SKE-
1091


WP_007209003
1038
--D----------- IINDD-GE-ILWNKQETIAQVIKTLG-MHQVNVVKKVEIQK GGFSK ESIQ-PKG-
1089


WP_023519017
1034
--E----------I ICDEQ-GE-VIWNKKRDLSTIKKTIG-AHQVNIVKKVEKQK GGFYK ETIN-SKA-
1085


WP_010770040
1046
--A----------V IIDEN-GE-ILWDK-KNIATVKKVMS-YPQMNIVKKPEIQT GSFSK ETIK-PKG-
1096


WP_048604708
1043
--K----------V IIDEN-GE-ILWNQ-KKIVTVKKVMN-YRQMNIVKKVEIQK GGFSK ESIL-PKG-
1093


WP_010750235
1043
--E----------Q FCDEN-GE-IFWDKRKHIQQIKKVIS-SHQVNIVKKVEVQT GSFYK ETVN-TKE-
1094


AIII6583
1091
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1153


WP_029073316
1053
--D----------- ----T-GE-VVWDP-EWISRIKKCFY-YKDCFVTKKLEENN GSFFN -TVR-PNDe
1099


WP_031589969
1053
--D----------- ----T-GE-IVWDP-NYIDRIKKCFY-YKDCFVTKKLEENN GTFFN -TVL-PNDt
1099


KDA45870
1035
YPF----------- -----------WDKARDLPTIKRYLY-RAQVNKVRKAERQT GGFSD EMLV-PKS-
1078


WP_039099354
1044
-------------E LVDEN-TEaVIWNKESGLAYLNKIYQ-FKKILVTREVHENS GALFN QTLYaAKDd
1097


AKP02966
1063
--N-------GTTQ --DRNtGE-IIWNVG-FRDKILKIFN-YHQCNVTRKTEIKT GQFYD QTIYsPKNp
1118


WP_010991369
1045
--D----------R IIDEN-GE-ILWDK-KYLDTVKKVMS-YRQMNIVKKTEIQK GEFSK ATIK-PKG-
1095


WP_033838504
1045
--D----------R IIDEN-GE-ILWDK-KYLDTVKKVMS-YRQMNIVKKTEIQK GEFSK ATIK-PKG-
1095


EHN60060
1048
--D----------R IIDEN-GE-ILWDK-KYLDTVKKVMS-YRQMNIVKKTEIQK GEFSK ATIK-PKG-
1098


EFR89594
814
--D----------R IIDEN-GE-ILWDK-KYLDTVKKVMS-YRQMNIVKKTEIQK GEFSK ATIK-PKG-
864


WP_038409211
1045
--N----------Q IIDKN-GE-ILWDN-RYLDTIKKVLS-YRQMNIVKKTEIQK GEFSN ATVN-PKG-
1095


EFR95520
664
--N----------Q IIDKN-GE-ILWDN-RYLDTIKKVLS-YRQMNIVKKTEIQK GEFSN ATVN-PKG-
714


WP_003723650
1045
--E----------R IIDEN-GE-ILWDK-KYLETIKKVLD-YRQMNIVKKTEIQK GEFSK ATIK-PKG-
1095


WP_003727705
1045
--E----------R IIDEN-GE-ILWDK-KYLETIKKVLD-YRQINIVKKTEIQK GEFSK ATIK-PKG-
1095


WP_003730785
1045
--E----------R IIDEN-GE-ILWDK-KYLETIKKVLD-YRQINIVKKTEIQK GEFSK ATIK-PKG-
1095


WP_003733029
1045
--D----------R IIDEN-GE-ILWDK-RYLETVKKVLG-YRQMNIVKKTEIQK GEFSN VTPN-PKG-
1095


WP_003739838
1045
--E----------R IIDEN-GE-ILWDK-KYLETIKKVLD-YRQMNIVKKTEIQK GEFSK ATIK-PKG-
1095


WP_014601172
1045
--E----------R IIDEN-GE-ILWDK-KYLETIKKVLD-YRQMNIVKKTEIQK GEFSK ATIK-PKG-
1095


WP_023548323
1045
--E----------R IIDEN-GE-ILWDK-KYLETIKKVLN-YRQMNIVKKTEIQK GEFSN QNPK-PRG-
1095


WP_031665337
1045
--E----------R IIDEN-GE-ILWDK-KYLETIKKVLD-YRQMNIVKKTEIQK GEFSK ATIK-PKG-
1095


WP_031669209
1045
--D----------R IIDEN-GE-ILWDK-RYLETVKKVLG-YRQMNIVKKTEIQK GEFSN VTPN-PKG-
1095


WP_033920898
1045
--E----------R IIDEN-GE-ILWDK-KYLETIKKVLN-YRQMNIVKKTEIQK GEFSN QNPK-PRG-
1095


AKI42028
1048
--E----------R IIDEN-GE-ILWDK-KYLETIKKVLD-YRQMNIVKKTEIQK GEFSK ATIK-PKG-
1098


AKI50529
1048
--E----------R IIDEN-GE-ILWDK-KYLETIKKVLN-YRQMNIVKKTEIQK GEFSN QNPK-PRG-
1098


EFR83390
493
--E----------R IIDEN-GE-ILWDK-KYLETIKKVLD-YRQMNIVKKTEIQK GEFSK ATIK-PKG-
543


WP_046323366
1045
--D----------R IIDEN-GE-ILWDK-KYLDTIKKVLN-YRQMNIVKKTEIQK GEFSN ATAN-PKG-
1095


AKE81011
1068
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
130


CUO82355
1043
--D----------- ------GK-LIWNP-DLINEIKKCFY-YKDCYCTTKLDQKS GQMFN -TVL-PNDa
1088


WP_033162887
1043
--D----------- ----T-GE-VMWDP-AKIGKIKSCFY-YKDVYVTKKLEQNS GTLFN -TVL-PNDa
1089


AGZ01981
1085
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1147


AKA60242
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


AKS40380
1052
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1114


4UN5_B
1056
LAN-GEIRKRPLIE TNGET-GE-IVWDKGRDFATVRKVLS-MPQVNIVKKTEVQT GGFSK ESIL-PKR-
1118


WP_010922251
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


WP_039695303
1121
--DSD KLIPRKTkKV-YW-DTKKYGGFDSPTVAYSV-FVVAD--VE--KGKAKKLKTVKELVGISIME RSFFEE
1185


WP_045635197
1119
--NSD KLIPRKT-KDILL-DTTKYGGFDSPVIAYSI-LLIAD--IE--KGKAKKLKTVKTLVGITIME KAAFEE
1183


5AXW_A
853
--EKN -LYKYYEeTGNYL---TKYSKKDNGPVIKKI------------KYYGNKLNAHLDITDDYPNS -VKLSL
912


WP_009880683
799
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELVGITIME RSSFEK
860


WP_010922251
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


WP_011054416
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


WP_011284745
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


WP_011285506
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


WP_011527619
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


WP_012560673
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELVGITIME RSSFEK
1176


WP_014407541
1114
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1175


WP_020905136
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGLTIME RSSFEK
1176


WP_023080005
1114
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1175


WP_023610282
1114
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1175


WP_030125963
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


WP_030126706
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


WP_031488318
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


WP_032460140
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELVGITIME RSSFEK
1176


WP_032461047
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELVGITIME RSSFEK
1176


WP_032462016
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


WP_032462936
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


WP_032464890
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


WP_033888930
940
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1001


WP_038431314
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


WP_038432938
1114
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1175


WP_038434062
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


BAQ51233
1026
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1087


KGE60162
290
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
351


KGE60856
53
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
114


WP_002989955
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


WP_003030002
1094
--ESD KLIPRKT-KNSYW-NPKKYGGFDSPVVAYSI-LVFAD--VE--KGKSKKLRKVQDMVGITIME KKRFEK
1158


WP_003065552
1122
--DSD KLIPRKTkKA-YW-DTKKYGGFDSPTVAYSV-FVVAD--VE--KGKAKKLKTVKELVGISIME RSFFEE
1186


WP_001040076
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040078
1121
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSKFEK
1185


WP_001040080
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040081
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040083
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040085
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040087
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040088
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040089
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040090
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040091
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040092
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVLAD--IK--KGKAQKLKTVKELIGITIME RERFEK
1177


WP_001040094
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040095
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040096
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040097
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040098
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040099
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPKVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040100
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040104
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040105
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_001040106
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RFRFEK
1177


WP_001040107
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RFRFEK
1177


WP_001040108
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RFRFEK
1177


WP_001040109
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RFRFEK
1177


WP_001040110
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RFRFEK
1177


WP_015058523
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVLAD--IK--KGKAQKLKTVKELIGITIME RERFEK
1177


WP_017643650
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_017647151
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_017648376
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_017649527
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_017771611
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RFRFEK
1177


WP_017771984
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVAAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


CFQ25032
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


CFV16040
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


KLJ37842
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


KLJ72361
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


KLL20707
1127
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1191


KLL42645
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RFRFEK
1177


WP_047207273
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_047209694
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_050198062
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_050201642
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_050204027
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RFRFEK
1177


WP_050881965
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_050886065
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


AHN30376
1113
--NSD KLIPRKT-KDIYL-DPKKYGGEDSPIVAYSV-LVLAD--IK--KGKAQKLKTVKELIGITIME RERFEK
1177


EA078426
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


CCW42055
1113
--NSD KLIPRKT-KDIYL-DPKKYGGFDSPIVAYSV-LVVAD--IK--KGKAQKLKTVTELLGITIME RSRFEK
1177


WP_003041502
1123
--DSS ENLVGVK-RNL---DPKKYGGYAGISNSYAV-LVKAI--IE--KGVKKKETMVLEFQGISILD RITFEK
1185


WP_037593752
1095
--ESD KLIPRKT-KNSYW-NPKKYGGFDSPVVAYSI-LVFAD--VE--KGKSKKLRKVQDMVGITIME KKRFEK
1159


WP_049516684
1095
--ESD KLIPRKT-KNSYW-NPKKYGGFDSPVVAYSI-LVFAD--VE--KGKSKKLRKVQDMVGITIME KKRFEK
1159


GAD46167
1094
--ESD KLIPRKT-KNSYW-NPKKYGGFDSPVVAYSI-LVFAD--VE--KGKSKKLRKVQDMVGITIME KKRFEK
1158


WP_018363470
1126
--DSD KLIPRKTkKV-LW-EPKKYGGEDSPTVAYSV-LVVAD--VE--KGKTKKLKTVKELVGISIME RSFFEK
1190


WP_003043819
1124
--ESA KLIP----RKKGW-DTRKYGGFGSPTVAYSI-LVVAK--VE--KGKAKKLKSVKVLVGITIME KGSYEK
1185


WP_006269658
1094
--ESD KLIPRKT-KNSYW-DPKKYGGFDSPVVAYSI-LVFAD--VE--KGKSKKLRKVQDMVGITIME KKRFEK
1158


WP_048800889
1114
--DSD KLIARKTkEN-YW-DTKKYGGEDSPTVAYSV-LVVAD--IK--KGKAKKLKTVKELVGISIME RPFFEK
1178


WP_012767106
1114
--SFD KLIS----RKHRF-ESSKYGGEGSPTVTYSV-LVVAKskVQ--DGKVKKIKTGKELIGMTLLD KLVFEK
1177


WP_014612333
1114
--SFD KLIS----RKHRF-ESSKYGGEGSPTVTYSV-LVVAKskVQ--DGKVKKIKTGKELIGITLLD KLVFEK
1177


WP_015017095
1114
--SFD KLIS----RKHRF-ESSKYGGEGSPTVTYSV-LVVAKskVQ--DGKVKKIKTGKELIGITLLD KLVFEK
1177


WP_015057649
1114
--SFD KLIS----RKHRF-ESSKYGGEGSPTVTYSV-LVVAKskVQ--DGKVKKIKTGKELIGITLLD KLVFEK
1177


WP_048327215
1114
--SFD KLIS----RKHRF-ESSKYGGEGSPTVTYSV-LVVAKckVQ--DGKVKKIKTGKELIGITLLD KLVFEK
1177


WP_049519324
1114
--SFD KLIS----RKHRF-ESSKYGGEGSPTVTYSV-LVVAKskVQ--DGKVKKIKTGKELIGITLLD KLVFEK
1177


WP_012515931
1095
--NSD KLIP----RKNNW-DTRKYGGFDSPTVAYSV-LVIAK--ME--KGKAKVLKPVKEMVGITIME RTAFEE
1156


WP_021320964
1095
--NSD KLIP----RKNNW-DTRKYGGFDSPTVAYSV-LVIAK--ME--KGKAKVLKPVKEMVGITIME RIAFEE
1156


WP_037581760
1095
--NSD KLIP----RKNNW-DTRKYGGFDSPTVAYSV-LVIAK--ME--KGKAKVLKPVKEMVGITIME RIAFEE
1156


WP_004232481
1124
--DSD KLIPRKTkKL-QW-ETQKYGGEDSPTVAYSV-LVVAD--VE--KGKTRKLKTVKELVGISIME RSSFEE
1188


WP_009854540
1119
--DSD KLIPRKTkKV-YW-DTKKYGGEDSPTVAYSV-FVVAD--VE--KGKAKKLKTVKELVGISIME RSFFEE
1183


WP_012962174
1120
--NSD KLIPRKTkKF-RW-DTPKYGGEDSPNIAYSV-FVIAD--VE--KGKAKKLKTVKELVGISIME RSSFEE
1184


WP_039695303
1121
--DSD KLIPRKTkKV-YW-DTKKYGGFDSPTVAYSV-FVVAD--VE--KGKAKKLKTVKELVGISIME RSFFEE
1185


WP_014334983
1124
--DSD KLIPRKTkKV-YW-NTKKYGGFDSPTVAYSV-LVVAD--IE--KGKAKKLKTVKELVGISIME RSFFEE
1188


WP_003099269
1115
--DSD KLIA----RKKSW-DPKKYGGFDSPIIAYSV-LVVAK--IA--KGKTQKLKTIKELVGIKIME QDEFEK
1176


AHY15608
1115
--DSD KLIA----RKKSW-DPKKYGGFDSPIIAYSV-LVVAK--IA--KGKTQKLKTIKELVGIKIME QDEFEK
1176


AHY17476
1115
--DSD KLIA----RKKSW-DPKKYGGFDSPIIAYSV-LVVAK--IA--KGKTQKLKTIKELVGIKIME QDEFEK
1176


ESR09100
1
----- -------------------------------------------------------------ME QDEFEK
8


AGM98575
1115
--DSD KLIA----RKKSW-DPKKYGGFDSPIIAYSV-LVVAK--IA--KGKTQKLKTIKELVGIKIME QDEFEK
1176


ALF27331
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAN--IE--KGKSKKLKLVKDLVGITIME RTIFEK
1158


WP_018372492
1109
---NN KLIP----RKKDW-SVDKYGGFIEPAESYSLaIFYTD--IN-----GKKPKKKSTIIAISRME KKDYEK
1167


WP_045618028
1125
vvDAS KLTPIKS-G---L-SPEKYGGYARPTIAYSV-LVIAD--IE--KGKAKKLKRIKEMVGITVQD KKKFEA
1188


WP_045635197
1119
--NSD KLIPRKT-KDILL-DTTKYGGFDSPVIAYSI-LLIAD--IE--KGKAKKLKTVKTLVGITIME KAAFEE
1183


WP_002263549
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002263887
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002264920
1094
--DSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002269043
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002269448
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002271977
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002272766
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002273241
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002275430
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002276448
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002277050
1112
--PLE KLVPLKK----AL-NPEKYGGYQKPTTAYPI-LLIVD---------------TKQLIPISVMD KKRFEQ
1166


WP_002277364
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002279025
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002279859
1094
--DSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002280230
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002281696
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002282247
1112
--PLE KLVPLKK----AL-NPEKYGGYQKPTTAYPI-LLIVD---------------TKQLIPISVMD KKRFEQ
1166


WP_002282906
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002283846
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002287255
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002288990
1094
--NSY KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002289641
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002290427
1094
--DSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002295753
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002296423
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002304487
1108
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1172


WP_002305844
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002307203
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002310390
1094
--DSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_002352408
1094
--DSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_012997688
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_014677909
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_019312892
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_019313659
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_019314093
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_019315370
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_019803776
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_019805234
1094
--DSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_024783594
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KSKSKKLKTVKALVGVTIME KMTFER
1158


WP_024784288
1112
--PLE KLVPLKK----AL-NPEKYGGYQKPTTAYPI-LLIVD---------------TKQLIPISVMD KKRFEQ
1166


WP_024784666
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_024784894
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_024786433
1112
--PLE KLVPLKK----AL-NPEKYGGYQKPTTAYPI-LLIVD---------------TKQLIPISVMD KKRFEQ
1166


WP_049473442
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


WP_049474547
1094
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1158


EMC03581
1087
--NSD KLIPRKT-KKFYW-DTKKYGGFDSPIVAYSI-LVIAD--IE--KGKSKKLKTVKALVGVTIME KMTFER
1151


WP_000428612
1122
--NSD KLIPRKT-KDILW-DTTKYGGFDSPVIAYSI-LLIAD--IE--KGKAKRLKTVKTLVGITIME KATFEK
1186


WP_000428613
1120
--NSD KLIPRKT-KDILW-ETTKYGGFDSPVIAYSI-LLIAD--IE--KGKAKKLKTVKTLVGITIME KAAFEE
1184


WP_049523028
1115
--NSD KLIPRKT-KNVQL-DTTKYGGFDSPVIAYSI-LLVAD--VE--KGKSKKLKTVKSLIGITIME KVKFEA
1179


WP_003107102
1084
--DSD KLIP----RKNNW-DPKKYGGFGSPIIAYSV-LVVAK--VT--KGKSQKTKSVKELVGITIME QNEFEK
1145


WP_054279288
1116
--KSS KLIP----RKNKWrDTTKYGGFNTPTVAYSV-LVVAK--VE--KGKAKKLKPVKELVGITIME RTKFEA
1178


WP_049531101
1125
vvDAS KLIPIKS-G---L-SPEKYGGYARPTIAYSV-LVIAD--IE--KGKAKKLKRIKEMVGITIQD KKKFEA
1188


WP_049538452
1125
vvDAS KLIPIKS-G---L-SPEKYGGYARPTIAYSV-LVIAD--IE--KGKTKKLKRIKEMIGITVQD KKIFES
1188


WP_049549711
1127
vvDAS KLIPIKS-G---L-SPEKYGGYARPTIAYSV-LVIAD--IE--KGKTKKLKRIKEMVGITIQD KKKFEA
1190


WP_007896501
1121
--NSD KLIE----RKKGW-DPKKYGGFDSPNTAYSI-FVVAK--VA--KRKAQKLKTVKEIVGITIME QAEYEK
1182


EFR44625
1073
--NSD KLIE----RKKGW-DPKKYGGFDSPNTAYSI-FVVAK--VA--KRKAQKLKTVKEIVGITIME QAEYEK
1134


WP_002897477
1119
--NSD KLIPRKT-KDILW-DTTKYGGFDSPVIAYSI-LLIAD--IE--KGKAKKLKTVKTLVGITIME KAAFEE
1183


WP_002906454
1124
vvDAS KLIPIKS-S---L-SPEKYGGYARPTIAYSV-LVIAD--IEkgKGKAKKLKRIKEIVGITIQD KKKFES
1189


WP_009729476
1120
--NSD KLIPRKT-KDILW-DTTKYGGFDSPVIAYSI-LLIAD--IE--KGKAKKLKTVKTLVGITIME KDAFEK
1184


CQR24647
1110
--GSD KLIARKT-KNNYL-STQKYGGFDSPTVAYSI-MFVAD--IE--KGKSKRLKTVKEMIGITIME RSRFES
1174


WP_000066813
1124
--NSD KLIPRKT-KEILW-DTTKYGGFDSPVIAYSI-LLIAD--IE--KGKAKKLKTVKTLVGITIME KATFEK
1188


WP_009754323
1120
--NSD KLIPRKT-KDILW-DTTKYGGFDSPVIAYSI-LLIAD--IE--KGKAKKLKTVKTLVGITIME KAAFEK
1184


WP_044674937
1113
--DSD KLIPRKT-EKFYL-DTKKYGGFDSPTIAYSV-LLIAD--IE--KGKAKKLKRVKELIGITIME RMAFEK
1177


WP_044676715
1115
--DSD KLIPRKT-EKFYL-DTKKYGGFDSPTIAYSV-LLIAD--IE--KGKAKKLKRVKELIGITIME RMAFEK
1179


WP_044680361
1115
--DSD KLIPRKT-EKFYL-DTKKYGGFDSPTIAYSV-LLIAD--IE--KGKAKKLKRVKELIGITIME RMAFEK
1179


WP_044681799
1113
--DSD KLIPRKT-EKFYL-DTKKYGGFDSPTIAYSV-LLIAD--IE--KGKAKKLKRVKELIGITIME RMAFEK
1177


WP_049533112
1123
--DSS ENLVGVK-RNL---DPKKYGGYAGISNSYAV-LVKAI--IE--KGVKKKETMVLEFQGISILD RITFEK
1185


WP_029090905
1062
--SSS KTIP----LKKHL-DTAIYGGYTAVNYASYA---LIQ--FK----KGRKLK--REIIGIPLAV QTRIDN
1117


WP_006506696
1085
haDKG AVVP---vNKNRS-DVHKYGGFSG--LQYTI----VA--IEggKKKGKKTELVKKISGVPLHL KAASIN
1149


AIT42264
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


WP_034440723
1093
k-KTE KRIP----IKNNL-DPNIYGGYIEEKMAYYI----AInyLE--NGKTKK-----AIVGISIKD KKDFEG
1149


AKQ21048
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


WP_004636532
1093
--DSS KLIP----VKEGM-DPQKYGGLSQVSEAFAV-VIT----HE--KGKKKQLK--SDLISIPIVD QKAYEQ
1150


WP_002364836
1099
--PSN KLIP----VKNGL-DPQKYGGFDSPIVAYTV-LF--T--HE--KGK-KPL-IKQEILGITIME KTRFEQ
1156


WP_016631044
1050
--PSN KLIP----VKNGL-DPQKYGGFDSPVVAYTV-LF--T--HE--KGK-KPL-IKQEILGITIME KTRFEQ
1107


EMS75795
835
--KPD KLIQ----RKAGW-DVSKYGGFGSPVVAYAV-AFI----YE--KGKAR--KKAKAIEGITIMK QSLFEQ
892


WP_002373311
1099
--PSN KLIP----VKNGL-DPQKYGGFDSPVVAYTV-LF--T--HE--KGK-KPL-IKQEILGITIME KTRFEQ
1156


WP_002378009
1099
--PSN KLIP----VKNGL-DPQKYGGFDSPIVAYTV-LF--T--HE--KGK-KPL-IKQEILGITIME KTRFEQ
1156


WP_002407324
1099
--PSN KLIP----VKNGL-DPQKYGGFDSPIVAYTV-LF--T--HE--KGK-KPL-IKQEILGITIME KTRFEQ
1156


WP_002413717
1099
--PSN KLIP----VKNGL-DPQKYGGFDSPVVAYTV-LF--T--HE--KGK-KPL-IKQEILGITIME KTRFEQ
1156


WP_010775580
1101
--PSN KLIP----VKNGL-DPQKYGGFDSPVVAYTV-LF--T--HE--KGK-KPL-IKQEILGITIME KTRFEQ
1158


WP_010818269
1099
--PSN KLIP----VKNGL-DPQKYGGFDSPIVAYTV-LF--T--HE--KGK-KPL-IKQEILGITIME KTRFEQ
1156


WP_010824395
1099
--PSN KLIP----VKNGL-DPQKYGGFDSPVVAYTV-LF--T--HE--KGK-KPL-IKQEILGITIME KTRFEQ
1156


WP_016622645
1099
--PSN KLIP----VKNGL-DPQKYGGFDSPIVAYTV-LF--T--HE--KGK-KPL-IKQEILGITIME KTRFEQ
1156


WP_033624816
1099
--PSN KLIP----VKNGL-DPQKYGGFDSPVVAYTV-LF--T--HE--KGK-KPL-IKQEILGITIME KTRFEQ
1156


WP_033625576
1099
--PSN KLIP----VKNGL-DPQKYGGFDSPVVAYTV-LF--T--HE--KGK-KPL-IKQEILGITIME KTKFEQ
1156


WP_033789179
1099
--PSN KLIP----VKNGL-DPQKYGGFDSPVVAYTV-LF--T--HE--KGK-KPL-IKQEILGITIME KTRFEQ
1156


WP_002310644
1101
--DSS KLLP----RKNNW-DPAKYGGLGSPNVAYTV-AFT----YE--KGKAR--KRTNALEGITIME REAFEQ
1158


WP_002312694
1102
--DSS KLLP----RKNNW-DPAKYGGLGSPNVAYTV-AFT----YE--KGKAR--KRTNALEGITIME REAFEQ
1159


WP_002314015
1102
--DSS KLLP----RKNNW-DPAKYGGLGSPNVAYTV-AFT----YE--KGKAR--KRTNALEGITIME REAFEQ
1159


WP_002320716
1102
--DSS KLLP----RKNNW-DPAKYGGLGSPNVAYTV-AFT----YE--KGKAR--KRTNALEGITIME REAFEQ
1159


WP_002330729
1101
--DSS KLLP----RKNNW-DPAKYGGLGSPNVAYTV-AFT----YE--KGKAR--KRTNALEGITIME REAFEQ
1158


WP_002335161
1102
--DSS KLLP----RKNNW-DPAKYGGLGSPNVAYTV-AFT----YE--KGKAR--KRTNALEGITIME REAFEQ
1159


WP_002345439
1102
--DSS KLLP----RKNNW-DPTKYGGLGSPNVAYTV-AFT----YE--KGKAR--KRTNALEGITIME REAFEQ
1159


WP_034867970
1092
--KPD KLIE----RKNNW-DVTKYGGFGSPVIAYAI-AFV----YA--KGKTQ--KKTRAIEGITIME QAAFEK
1149


WP_047937432
1102
--DSS KLLP----RKNNW-DPAKYGGLGSPNVAYTV-AFT----YE--KGKAR--KRTNALEGITIME REAFEQ
1159


WP_010720994
1092
--KPD KLIE----RKNNW-DVTKYGGFGSPVIAYAI-AFV----YA--KGKTQ--KKTKAIEGITIME QAAFEK
1149


WP_010737004
1092
--KPD KLIE----RKNNW-DVTKYGGFGSPVIAYAI-AFV----YA--KGKTQ--KKTRAIEGITIME QAAFEK
1149


WP_034700478
1092
--KPD KLIE----RKNNW-DVTKYGGFGSPVIAYAI-AFV----YA--KGKTQ--KKTRAIEGITIME QAAFEK
1149


WP_007209003
1090
--ESQ KLIR----RKQQW-NTKKYGGFDSPVVAYAI---LLS--FD--KGK-RKARSFK-IVGITIQD RESFEG
1147


WP_023519017
1086
--NPE KLIP----RKASL-DPLKYGGYGSPLVAYTV-IFI----FE--KGKQK--KVTKGIEGITVME QLRFEQ
1143


WP_010770040
1097
--DSD KLIS----RKTNW-SPKLYGGFDSPQVAYSV-II--T--YE--KGK-KKVRA-KAIVGITIME QSLFKK
1154


WP_048604708
1094
--DSD KLIS----RKKEW-DTTKYGGFDSPNVAYSV-VI--R--YE--KGK-TRKLV-KTIVGITIME RAAFEK
1151


WP_010750235
1095
--KPD KLIK----RKNNW-DVTKYGGFGSPVVAYAV-VFT----YE--KGKNH--KKAKAIEGITIME QALFEK
1152


AII16583
1154
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1215


WP_029073316
1100
hsEKG AKVP---vNKLRS-NVHKYGGFEG--LKYSI----VA--IKgkKKKGKKIIDVNKLVGIPLMY KNVDDE
1164


WP_031589969
1100
nsDKD ATVP---vNKYRS-NVNKYGGFSG--VNSFI----VA--IKgkKKKGKKVIEVNKLTGIPLMY KNADEE
1164


KDA45870
1079
--DSG KLLP----RKEGL-DPVKYGGYAKAVESYAV-LITAD-eVK--KGKTKKVKT---LVNIPIID SKKYEA
1138


WP_039099354
1098
k-ASG QLIPAKQdRPTAL-----YGGYSGKTVAYMC---IVR--IKnkKGDLYKVCGVETSWLAQLKQ KKAFLK
1170


AKP02966
1119
k---- KLIA----QKKDM-DPNIYGGFSGDNKSSIT---IVK--ID-----NNKIKPVA--IPIRLIN ----DK
1172


WP_010991369
1096
--NSS KLIP----RKTNW-DPMKYGGLDSPNMAYAV-VI--E--YA--KGK-NKLVFEKKIIRVTIME RKAFEK
1154


WP_033838504
1096
--NSS KLIS----RKTNW-DPMKYGGLDSPNMAYAV-VI--E--YA--KGK-NKLVFEKKIIRVTIME RKAFEK
1154


EHN60060
1099
--NSS KLIS----RKTNW-DPMKYGGLDSPNMAYAV-VI--E--YA--KGK-NKLVFEKKIIRVTIME RKAFEK
1157


EFR89594
865
--NSS KLIP----RKTNW-DPMKYGGLDSPNMAYAV-VI--E--YA--KGK-NKLVFEKKIIRVTIME RKAFEK
923


WP_038409211
1096
--NSS KLIS----RKADW-NPIKYGGFDGSNMAYSI-VI--E--YE--KRK-KKTVIKKELIQINIME RVAFEK
1154


EFR95520
715
--NSS KLIS----RKADW-NPIKYGGFDGSNMAYSI-VI--E--YE--KRK-KKTVIKKELIQINIME RVAFEK
773


WP_003723650
1096
--NSS KLIP----RKENW-DPMKYGGLDSPNMAYAV-II--E--HA--KGK-KKIVIEKKLIQINIME RKMFEK
1154


WP_003727705
1096
--NSS KLIP----RKENW-DPMKYGGLDSPNMAYAV-II--E--HA--KGK-KKIVIEKKLIQINIME RKMFEK
1154


WP_003730785
1096
--NSS KLIP----RKENW-DPVKYGGLDSPNMAYAV-II--E--HA--KGK-KKIVIEKKLIQINIME RKMFEK
1154


WP_003733029
1096
--KSN KLIP----RKKDW-DPIKYGGFDGSKMAYAI-II--E--YE--KQK-RKVRIEKKLIQINIME REAFEK
1154


WP_003739838
1096
--NSS KLIP----RKENW-DPMKYGGLDSPNMAYAV-II--E--HA--KGK-KKVVFEKKIIRITIME RKAFEK
1154


WP_014601172
1096
--NSS KLIP----RKENW-DPMKYGGLDSPNMAYAV-II--E--HA--KGK-KKLIFEKKIIRITIME RKMFEK
1154


WP_023548323
1096
--DSS KLIP----KKTNL-NPIKYGGFEGSNMAYAI-II--E--HE--KRK-KKVTIEKKLIQINIME RKAFEK
1154


WP_031665337
1096
--NSS KLIP----RKENW-DPMKYGGLDSPNMAYAV-II--E--HA--KGK-KRIVIEKKLIQINIME RKMFEK
1154


WP_031669209
1096
--KSN KLIP----RKKDW-DPIKYGGFDGSKMAYAI-II--E--YE--KQK-RKVRIEKKLIQINIME REAFEK
1154


WP_033920898
1096
--DSS KLIP----KKTNL-NPIKYGGFEGSNMAYAI-II--E--HE--KRK-KKVTIEKKLIQINIME RKAFEK
1154


AKI42028
1099
--NSS KLIP----RKENW-DPMKYGGLDSPNMAYAV-II--E--HA--KGK-KKLIFEKKIIRITIME RKMFEK
1157


AKI50529
1099
--DSS KLIP----KKTNL-NPIKYGGFEGSNMAYAI-II--E--HE--KRK-KKVTIEKKLIQINIME RKAFEK
1157


EFR83390
544
--NSS KLIP----RKENW-DPMKYGGLDSPNMAYAV-II--E--HA--KGK-KKIVIEKKLIQINIME RKMFEK
602


WP_046323366
1096
--NSS KLIP----RKADW-DPIKYGGFDGSNMAYAI-VI--E--HE--KRK-KKTVIKKELIQINIME RTAFEK
1154


AKE81011
1131
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1192


CUO82355
1089
hsAKG AVIP---vNKNRK-DVNKYGGFSG--LQYVI----AA--IEgtKKKGKKLVKVRKLSGIPLYL KQADIK
1153


WP_033162887
1090
hsEKG ATVP---1NKYRA-DVHKYGGFGN--VQSII----VA--IEgkKKKGKKLIDVRKLTSIPLHL KNAPVE
1154


AGZ01981
1148
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1209


AKA60242
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


AKS40380
1115
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1176


4UN5_B
1119
--NSD KLIA----RKKDW-DPKKYGGFDSPTVAYSV-LVVAK--VE--KGKSKKLKSVKELLGITIME RSSFEK
1180


WP_010922251
1177
NPI---DFLE---AKGYKE--V-KKDLIIK--LPKYSLFE---LENGRKRMLAS -Gcustom character LQKGNELALPSKYVNFLYLA
1239


WP_039695303
1186
NPV---EFLE---NKGYHN--I-REDKLIK--LPKYSLFE---FEGGRRRLLAS ASELQKGNEMVLPGYLVELLYHA
1248


WP_045635197
1184
NPI---TFLE---NKGYHN--V-RKENILC--LPKYSLFE---LENGRRRLLAS AKELQKGNEIVLPVYLTTLLYHS
1246


5AXW_A
913
KPYrfdVYLD---NGVYKFvtV-KNLDVIK----KENYYE---VNSKAYEEAKK -KKISNQAEFIASFYNNDLIKIN
978


WP_009880683
861
DPV---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
923


WP_010922251
1177
NPI---DFLE---AKGYKE--V-KKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_011054416
1177
DPI---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_011284745
1177
NPI---DFLE---AKGYKE--V-RKDLIVK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_011285506
1177
NPI---DFLE---AKGYKE--V-KKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_011527619
1177
NPI---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_012560673
1177
DPV---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_014407541
1176
NPI---DFLE---AKGYKE--V-KKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1238


WP_020905136
1177
NPI---DFLE---AKGYKE--V-KKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_023080005
1176
NPI---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1238


WP_023610282
1176
NPI---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1238


WP_030125963
1177
NPI---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_030126706
1177
NPI---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_031488318
1177
NPI---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_032460140
1177
DPV---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_032461047
1177
DPV---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_032462016
1177
NPI---DFLE---AKGYKE--V-KKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_032462936
1177
NPI---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_032464890
1177
NPI---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_033888930
1002
NPI---DFLE---AKGYKE--V-KKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1064


WP_038431314
1177
NPI---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_038432938
1176
NPI---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1238


WP_038434062
1177
NPI---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


BAQ51233
1088
NPI---DFLE---AKGYKE--V-KKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1150


KGE60162
352
DPI---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
414


KGE60856
115
DPI---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
177


WP_002989955
1177
NPI---DFLE---AKGYKE--V-RKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_003030002
1159
HPV---DFLE---QRGYRN--V-RLEKIIK--LPKYSLFE---LENKRRRLLAS ARELQKGNELVIPQRFTTLLYHS
1221


WP_003065552
1187
NPV---EFLE---NKGYHN--I-REDKLIK--LPKYSLFE---FEGGKRRLLAS ASELQKGNEMVIPGHLVKLLYHA
1249


WP_001040076
1178
NPS---AFLE---SKGYLN--I-RTDKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_001040078
1186
NPS---AFLE---SKGYLN--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1248


WP_001040080
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_001040081
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGETIDRLQKGNELALPTQFMKFLYLA
1240


WP_001040083
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_001040085
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_001040087
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_001040088
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_001040089
1178
NPS---AFLE---SKGYLN--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_001040090
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_001040091
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_001040092
1178
NPS---AFLE---SKGYLN--I-RTDKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQYMKFLYLA
1240


WP_001040094
1178
NPS---AFLE---SKGYLN--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_001040095
1178
NPS---AFLE---SKGYLN--I-RTDKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQYMKFLYLA
1240


WP_001040096
1178
NPS---AFLE---SKGYLN--I-RTDKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQYMKFLYLA
1240


WP_001040097
1178
NPS---AFLE---SKGYLN--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS ADELQKGNELALPTQFMKFLYLA
1240


WP_001040098
1178
NPS---AFLE---SKGYLN--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_001040099
1178
NPS---AFLE---SKGYLN--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_001040100
1178
NPS---AFLE---SKGYLD--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_001040104
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_001040105
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_001040106
1178
NPS---AFLE---SKGYLN--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQYMKFLYLA
1240


WP_001040107
1178
NPS---AFLE---SKGYLN--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQYMKFLYLA
1240


WP_001040108
1178
NPS---AFLE---SKGYLN--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQYMKFLYLA
1240


WP_001040109
1178
NPS---AFLE---SKGYLN--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQYMKFLYLA
1240


WP_001040110
1178
NPS---AFLE---SKGYLN--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQYMKFLYLA
1240


WP_015058523
1178
NPS---AFLE---SKGYLN--I-RTDKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQYMKFLYLA
1240


WP_017643650
1178
NPS---AFLE---SKGYLN--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS ADELQKGNELALPTQFMKFLYLA
1240


WP_017647151
1178
NPS---AFLE---SKGYLN--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_017648376
1178
NPS---AFLE---SKGYLN--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_017649527
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_017771611
1178
NPS---AFLE---SKGYLN--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQYMKFLYLA
1240


WP_017771984
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


CFQ25032
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


CFV16040
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


KLJ37842
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


KLJ72361
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


KLL20707
1192
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1254


KLL42645
1178
NPS---AFLE---SKGYLN--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQYMKFLYLA
1240


WP_047207273
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_047209694
1178
NPS---AFLE---SKGYLN--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_050198062
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_050201642
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_050204027
1178
NPS---AFLE---SKGYLN--I-RDDKLMI--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQYMKFLYLA
1240


WP_050881965
1178
NLS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_050886065
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


AHN30376
1178
NPS---AFLE---SKGYLN--I-RTDKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQYMKFLYLA
1240


EA078426
1178
NPS---AFLE---SKGYLN--I-RADKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


CCW42055
1178
NPS---AFLE---SKGYLN--I-RTDKLII--LPKYSLFE---LENGRRRLLAS AGELQKGNELALPTQFMKFLYLA
1240


WP_003041502
1186
DKR---AFLL---GKGYKD--I-K--KIIE--LPKYSLFE---LKDGSRRMLAS RGEIHKGNELFVPQKFTTLLYHA
1253


WP_037593752
1160
NPV---DFLE---QRGYRN--V-RLEKIIK--LPKYSLFE---LENKRRRLLAS ARELQKGNELVIPQRFTTLLYHS
1222


WP_049516684
1160
HPV---DFLE---QRGYRN--V-RLEKIIK--LPKYSLFE---LENKRRRLLAS ARELQKGNELVIPQRFTTLLYHS
1222


GAD46167
1159
NPV---DFLE---QRGYRN--V-RLEKIIK--LPKYSLFE---LENKRRRLLAS ARELQKGNELVIPQRFTTLLYHS
1221


WP_018363470
1191
NPV---EFLK---NKGYQN--V-QEDKLMK--LPKYSLFE---FEGGRRRLLAS ATELQKGNEIMLSAHLVALLYHA
1253


WP_003043819
1186
DPI---GFLE---AKGYKD--I-KKELIFK--LPKYSLFE---LENGRRRMLAS --ELQKANELVLPQHLVRLLYYT
1248


WP_006269658
1159
NPV---DFLE---QRGYRN--V-RLEKIIK--LPKYSLFE---LENKRRRLLAS AKELQKGNELVIPQRFTTLLYHS
1221


WP_048800889
1179
NPI---MFLE---SKGYRN--I-QKDKLIK--LPKYSLFE---FEGGRRRLLAS AVELQKGNEMVLPQYLNNLLYHA
1241


WP_012767106
1178
NPL---KFIE---DKGYGN--V-QIDKCIK--LPKYSLFE---FENGTRRMLAS RGDLQKANEMFLPAKLVTLLY--
1245


WP_014612333
1178
NPL---KFIE---DKGYGN--V-QIDKCIK--LPKYSLFE---FENGTRRMLAS RGDLQKANEMFLPAKLVTLLY--
1245


WP_015017095
1178
NPL---KFIE---DKGYGN--V-QIDKCIK--LPKYSLFE---FENGTRRMLAS RGDLQKANEMFLPAKLVTLLY--
1245


WP_015057649
1178
NPL---KFIE---DKGYGN--V-QIDKCIK--LPKYSLFE---FENGTRRMLAS RGDLQKANEMFLPAKLVTLLY--
1245


WP_048327215
1178
NPL---KFIE---DKGYGN--V-QIDKCIK--LPKYSLFE---FENGTRRMLAS RGDLQKANEMFLPAKLVTLLY--
1245


WP_049519324
1178
NPL---KFIE---DKGYGN--V-QIDKCIK--LPKYSLFE---FENGTRRMLAS RGDLQKANEMFLPAKLVTLLY--
1245


WP_012515931
1157
NPV---VFLE---ARGYRE--I-QEHLIIK--LPKYSLFE---LENGRRRLLAS -SELQKGNELFLPVDYMTFLYLA
1219


WP_021320964
1157
NPV---VFLE---AKGYRE--I-QEHLIIK--LPKYSLFE---LENGRRRLLAS -SELQKGNELFLPVDYMTFLYLA
1219


WP_037581760
1157
NPV---VFLE---AKGYRE--I-QEHLIIK--LPKYSLFE---LENGRRRLLAS -SELQKGNELFLPVDYMTFLYLA
1219


WP_004232481
1189
NPV---SFLE---KKGYHN--V-QEDKLIK--LPKYSLFE---FEGGRRRLLAS ATELQKGNEVVLPQYMVNLLYHS
1251


WP_009854540
1184
NPV---EFLE---NKGYHN--I-REDKLIK--LPKYSLFE---FEGGRRRLLAS ASELQKGNEMVLPGYLVELLYHA
1246


WP_012962174
1185
NPV---VFLE---KKGYQN--V-QEDNLIK--LPKYSLFE---FEGGRRRLLAS ASELQKGNEVVLSRHLVELLYHA
1247


WP_039695303
1186
NPV---EFLE---NKGYHN--I-REDKLIK--LPKYSLFE---FEGGRRRLLAS ASELQKGNEMVLPGYLVELLYHA
1248


WP_014334983
1189
NPV---SFLE---KKGYHN--V-QEDKLIK--LPKYSLFE---FEGGRRRLLAS ATELQKGNEVMLPAHLVELLYHA
1251


WP_003099269
1177
DPI---AFLE---KKGYQD--I-QTSSIIK--LPKYSLFE---LENGRKRLLAS --ELQKGNELALPNKYVKFLYLA
1239


AHY15608
1177
DPI---AFLE---KKGYQD--I-QTSSIIK--LPKYSLFE---LENGRKRLLAS --ELQKGNELALPNKYVKFLYLA
1239


AHY17476
1177
DPI---AFLE---KKGYQD--I-QTSSIIK--LPKYSLFE---LENGRKRLLAS --ELQKGNELALPNKYVKFLYLA
1239


ESR09100
9
DPI---AFLE---KKGYQD--I-QTSSIIK--LPKYSLFE---LENGRKRLLAS -KELQKGNELALPNKYVKFLYLA
71


AGM98575
1177
DPI---AFLE---KKGYQD--I-QTSSIIK--LPKYSLFE---LENGRKRLLAS --ELQKGNELALPNKYVKFLYLA
1239


ALF27331
1159
NPV---AFLE---RKGYRN--V-QEENIVK--LPKYSLFE---LENGRRRLLAS ARELQKGNEIVLPNHLGTMLYHA
1221


WP_018372492
1168
EPEr---FLA---QKGFER--V-EKT--IK--LPKYSLFE---MEKGRRRLLAS SGELQKGNQVLLPEHLIRLLSYA
1228


WP_045618028
1189
NPI---AYLE---ECGYKN--I-NPNLIIK--LPKYSLFE---FNNGQRRLLAS SIELQKGNELIVPYHFTALLYHA
1251


WP_045635197
1184
NPI---TFLE---NKGYHN--V-RKENILC--LPKYSLFE---LENGRRRLLAS AKELQKGNEIVLPVYLTTLLYHS
1246


WP_002263549
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002263887
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002264920
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002269043
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002269448
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002271977
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002272766
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002273241
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002275430
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002276448
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002277050
1167
NPV---KFLK---DKGYQQ--I-EKNNFVK--LPKYTLVD---IGNGIKRLWAS SKEVHKGNQLVVSKKSQDLLYHA
1229


WP_002277364
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002279025
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002279859
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002280230
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002281696
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002282247
1167
NPV---KFLK---DKGYQQ--I-EKNNFVK--LPKYTLVD---IGNGIKRLWAS SKEVHKGNQLVVSKKSQDLLYHA
1229


WP_002282906
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002283846
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002287255
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002288990
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002289641
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002290427
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002295753
1159
DPI---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002296423
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002304487
1173
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLETLLYHA
1235


WP_002305844
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002307203
1159
DPI---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002310390
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_002352408
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPDHLGTLLYHA
1221


WP_012997688
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_014677909
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_019312892
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_019313659
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_019314093
1159
DPI---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_019315370
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_019803776
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_019805234
1159
DPI---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_024783594
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_024784288
1167
NPV---KFLK---DKGYQQ--I-EKNNFVK--LPKYTLVD---IGNGIKRLWAS SKEVHKGNQLVVSKKSQDLLYHA
1229


WP_024784666
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_024784894
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_024786433
1167
NPV---KFLK---DKGYQQ--I-EKNNFVK--LPKYTLVD---IGNGIKRLWAS SKEVHKGNQLVVSKKSQDLLYHA
1229


WP_049473442
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


WP_049474547
1159
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1221


EMC03581
1152
DPV---AFLE---RKGYRN--V-QEENIIK--LPKYSLFK---LENGRKRLLAS ARELQKGNEIVLPNHLGTLLYHA
1214


WP_000428612
1187
SPI---AFLE---NKGYHN--V-RKENILC--LPKYSLFE---LKNGRRRMLAS AKELQKGNEIVLPVHLTTLLYHA
1249


WP_000428613
1185
NPI---TFLE---NKGYHN--V-RKENILC--LPKYSLFE---LENGRRRLLAS AKELQKGNEIVLPVYLTTLLYHS
1247


WP_049523028
1180
NPV---AFLE---GKGYQN--V-VEENIIR--LPKYSLFE---LENGRRRMLAS AKELQKGNEMVLPSYLIALLYHA
1242


WP_003107102
1146
DRI---TFLE---KKGYQD--I-QESLIIK--LPKFSLFE---LENGRKRLLAS --ELQKGNELSLPNKYIQFLYLA
1208


WP_054279288
1179
NPI---AFLE---SKGYHD--I-QEHLMIT--LPKYSLFE---LENGRRRLLAS --ELQKGNEMVLPQHLVTFLYRV
1241


WP_049531101
1189
NPT---AYLE---EYGYKN--I-NPNLIIK--LPKYSLFK---FNDGQRRLLAS SIELQKGNELILPYHFTTLLYHA
1251


WP_049538452
1189
NPI---AYLE---ECGYKN--I-NPNLIIK--LPKYSLFE---FNGGQRRLLAS SIELQKGNELILPYHFTALLYHT
1251


WP_049549711
1191
NPI---AYLE---ECGYKN--I-NPNLIIK--LPKYSLFE---FNGGQRRLLAS SIELQKGNELILPYHFTALLYHA
1253


WP_007896501
1183
DNI---AFLE---KKGYQD--I-QEKLLIK--LPKYSLFE---LENGRRRLLAS --EFQKGNELALSGKYMKFLYLA
1245


EFR44625
1135
DNI---AFLE---KKGYQD--I-QEKLLIK--LPKYSLFE---LENGRRRLLAS --EFQKGNELALSGKYMKFLYLA
1197


WP_002897477
1184
NPI---TFLE---NKGYHN--V-RKENILC--LPKYSLFE---LENGRRRLLAS AKELQKGNEIVLPVCLTTLLYHS
1246


WP_002906454
1190
NPV---TYLE---ECGYKN--I-NSNLIIK--LPKYSLFE---FNDGQRRLLAS SIELQKGNELILPYHLTALLYHA
1252


WP_009729476
1185
NPI---AFLE---NKGYHN--V-CKENILC--LPKYSLFE---LENGRRRLLAS AKELQKCNEIVLPVYLTTLLYHS
1247


CQR24647
1175
NSV---TFLE---EKGYRN--I-RENTIIK--FPKYSLFE---LENGRRRLLAS AIELQKGNEMFLPQQFVNLLYHA
1237


WP_000066813
1189
NPI---TFLE---NKGYHN--V-RKENILC--LPKYSLFE---LESGRRRMLAS AKELQKGNEIVLPVYLTTLLYHS
1251


WP_009754323
1185
NPI---TFLE---NKGYHN--V-RKENILC--LPKYSLFE---LENGRRRLLAS AKELQKGNEIVLPVYLTTLLYHS
1247


WP_044674937
1178
NPI---EFLE---HKGYKN--I-LEKNIIK--LPKYSLFE---LENGRRRLLAS AKELQKGNEMILPPHLVTLLYHS
1240


WP_044676715
1180
NPI---EFLE---HKGYKN--I-LEKNIIK--LPKYSLFE---LENGRRRLLAS AKELQKGNEMILPPHLVTLLYHS
1242


WP_044680361
1180
NPI---EFLE---HKGYKN--I-LEKNIIK--LPKYSLFE---LENGRRRLLAS AKELQKGNEMILPPHLVTLLYHS
1242


WP_044681799
1178
NPI---EFLE---HKGYKN--I-LEKNIIK--LPKYSLFE---LENGRRRLLAS AKELQKGNEMILPPHLVTLLYHS
1240


WP_049533112
1186
DKR---AFLL---GKGYKD--I-K--KIIE--LPKYSLFE---LKDGSRRMLAS RGEIHKGNELFVPQKFTTLLYHA
1253


WP_029090905
1118
SETslqAYIA---EQIKSE--VeILN----grILKYQLIS----NNGNRLYIAG -SERHNARQLIVSDEAAKVIWLI
1181


WP_006506696
1150
EKI---NYIE--eKEGLSD--VrIIK---Dn-IPVNQMIEm----DGGEYLLTS --EYVNARQLVLNEKQCALIADI
1211


AIT42264
1177
NPI---DFLE---AKGYKE--V-KKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_034440723
1150
QTT---EYLG---KIGFNK--AsIIN---S--FKNYTLFE---LENGSRRMIVG KGELQKGNQMYLPQNLLEFVYHL
1217


AKQ21048
1177
NPI---DFLE---AKGYKE--V-KKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


WP_004636532
1151
HPT---AYLE---EAGYNN--P-TV--LHE--LFKYQLFE---LEDGSRRMIAS AKEFQKGNQMVLPLELVELLYHA
1211


WP_002364836
1157
NPI---LFLE---EKGFLR--P-RV--LMK--LPKYTLYE---FPEGRRRLLAS AKEAQKGNQMVLPEHLLTLLYHA
1217


WP_016631044
1108
NPI---LFLE---EKGFLR--P-RV--LMK--LPKYTLYE---FPEGRRRLLAS AKEAQKGNQMVLPEHLLTLLYHA
1168


EM575795
893
DPI---GFLS---NKGYSN--V-TKF--IK--LSKYTLYE---LENGRRRMVAS -KEAQKANSFILPEKLVTLLYHA
953


WP_002373311
1157
NPI---LFLE---EKGFLR--P-RV--LMK--LPKYTLYE---FPEGRRRLLAS AKEAQKGNQMVLPEHLLTLLYHA
1217


WP_002378009
1157
NPI---LFLE---EKGFLR--P-RV--LMK--LPKYTLYQ---FPEGRRRLLAS AKEAQKGNQMVLPEHLLTLLYHA
1217


WP_002407324
1157
NPI---LFLE---EKGFLR--P-RV--LMK--LPKYTLYE---FPEGRRRLLAS AKEAQKGNQMVLPEHLLTLLYHA
1217


WP_002413717
1157
NPI---LFLE---EKGFLR--P-RV--LMK--LPKYTLYE---FPEGRRRLLAS AKEAQKGNQMVLPEHLLTLLYHA
1217


WP_010775580
1159
NPI---LFLE---EKGFLR--P-RV--LMK--LPKYTLYE---FPEGRRRLLAS AKEAQKGNQMVLPEHLLTLLYHA
1219


WP_010818269
1157
NPI---LFLE---EKGFLR--P-RV--LMK--LPKYTLYE---FPEGRRRLLAS AKEAQKGNQMVLPEHLLTLLYHA
1217


WP_010824395
1157
NPI---LFLE---EKGFLR--P-RV--LMK--LPKYTLYE---FPEGRRRLLAS AKEAQKGNQMVLPEHLLTLLYHA
1217


WP_016622645
1157
NPI---LFLE---EKGFLR--P-RV--LMK--LPKYTLYE---FPEGRRRLLAS AKEAQKGNQMVLPEHLLTLLYHA
1217


WP_033624816
1157
NPI---LFLE---EKGFLR--P-RV--LMK--LPKYTLYE---FPEGRRRLLAS AKEAQKGNQMVLPERLLTLLYHA
1217


WP_033625576
1157
NPI---LFLE---EKGFLR--P-RV--LMK--LPKYTLYE---FPEGRRRLLAS AKEAQKGNQMVLPEHLLTLLYHA
1217


WP_033789179
1157
NPI---LFLE---EKGFLR--P-RV--LMK--LPKYTLYE---FPEGRRRLLAS AKEAQKGNQMVLPEHLLTLLYHA
1217


WP_002310644
1159
SPV---LFLK---NKGYEQ--A-EIE--MK--LPKYALFE---LENGRKRMVAS -KEAQKANSFLLPEHLVTLLYHA
1219


WP_002312694
1160
SPV---LFLK---NKGYEQ--A-EIE--MK--LPKYALFE---LENGRKRMVAS -KEAQKANSFLLPEHLVTLLYHA
1220


WP_002314015
1160
SPV---LFLK---NKGYEQ--A-EIE--MK--LPKYALFE---LENGRKRMVAS -KEAQKANSFLLPEHLVTLLYHA
1220


WP_002320716
1160
SPV---LFLK---NKGYEQ--A-EIE--MK--LPKYALFE---LENGRKRMVAS -KEAQKANSFLLPEHLVTLLYHA
1220


WP_002330729
1159
SPV---LFLK---NKGYEQ--A-EIE--MK--LPKYALFE---LENGRKRMVAS -KEAQKANSFLLPEHLVTLLYHA
1219


WP_002335161
1160
SPV---LFLK---NKGYEQ--A-EIE--MK--LPKYALFE---LENGRKRMVAS -KEAQKANSFLLPEHLVTLLYHA
1220


WP_002345439
1160
SPV---LFLK---NKGYEQ--A-EIE--MK--LPKYALFE---LENGRKRMVAS -KEAQKANSFLLPEHLVTLLYHA
1220


WP_034867970
1150
DPT---TFLK---EKGFPQ--V-TEF--IK--LPKYTLFE---FDNGRRRFLAS -KESQKGNPFILSDQLVTLLYHA
1210


WP_047937432
1160
SPV---LFLK---NKGYEQ--A-EIE--MK--LPKYALFE---LENGRKRMVAS -KEAQKANSFLLPEHLVTLLYHA
1220


WP_010720994
1150
DPT---TFLK---DKGFPQ--V-TEF--IK--LPKYTLFE---FDNGRRRFLAS -KESQKGNPFILSDQLVTLLYHA
1210


WP_010737004
1150
DPT---TFLK---EKGFPQ--V-TEF--IK--LPKYTLFE---FDNGRRRFLAS -KESQKGNPFILSDQLVTLLYHA
1210


WP_034700478
1150
DPT---TFLK---DKGFPH--V-TEF--IK--LPKYTLFE---FDNGRRRFLAS -KESQKGNPFILSDQLVTLLYHA
1210


WP_007209003
1148
NPI1---YLS---KKDYHN---pKVEAI----LPKYSLFE---FENGRRRMVAS -SETQKGNQLIIPGHLMELLYHS
1208


WP_023519017
1144
DPR---EFLK---TKGYEG--V-KQW--LI--LPKYILFE---AQGGYRRMIAS -QETQKANSLILPENLVTLLYHA
1204


WP_010770040
1155
DPV---SLLE---EKGYAN--P-EV--LIH--LPKYTLYE---LENGRRRLLAS ANEAQKGNQLVLPASLVTLLYHA
1215


WP_048604708
1152
NER---EFLK---NKGYQN--P-QI--CMK--LPKYSLYE---FDDGRRRLLAS AKEAQKGNQMVLPAHLVTFLYHA
1212


WP_010750235
1153
DPI---SFLI---EKGYSN--V-NQF--IK--LPKYTLFE---LANGQRRMLAS -QELQKANSFILPEKLVTLLYHA
1213


AII16583
1216
NPI---DFLE---AKGYKE--V-KKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1278


WP_029073316
1165
TKI---NYIK--eSEGLEE--VkIIK---E--ILKNQLIET----NGGLFYVTS --EIVNARQLILDFNCTRIIDGI
1225


WP_031589969
1165
IKI---NYLK--qAEDLEE--VqIGK---E--ILKNQLIEk----DGGLYYIVA --EIINAKQLILNESQTKLVCEI
1225


KDA45870
1139
DPT---AYLA---SRGYTNvtNsFIL-------PKYSLLEd---PEGRRRYLAS -KEFQKANELILPQHLVELLYWV
1199


WP_039099354
1171
QKI-spQFTKv---KKQKGtiV-KVVEDFEv-IAPHILINqrfFDNGQELTLGS ----HNEQELILDKTAVKLLNGA
1241


AKP02966
1173
KTL--qNWLE---ENVKHKksIqIIK---Nn-VPIGQIIY------SKKVGLLS -REIANRQQLILPPEHSALLRIL
1237


WP_010991369
1155
DEK---AFLE---EQGYRQ--P-KV--LAK--LPKYTLYE---CEEGRRRMLAS ANEAQKGNQQVLPNHLVTLLHHA
1215


WP_033838504
1155
DEK---AFLE---EQGYRQ--P-KV--LAK--LPKYTLYE---CEEGRRRMLAS ANEAQKGNQQVLPNHLVTLLHHV
1215


EHN60060
1158
DEK---AFLE---EQGYRQ--P-KV--LAK--LPKYTLYE---CEEGRRRMLAS ANEAQKGNQQVLPNHLVTLLHHV
1218


EFR89594
924
DEK---AFLE---EQGYRQ--P-KV--LAK--LPKYTLYE---CEEGRRRMLAS ANEAQKGNQQVLPNHLVTLLHHA
984


WP_038409211
1155
DQK---AFLE---EKGYYS--P-KV--LTK--IPKYTLYE---CENGRRRMLGS ANEAQKGNQMVLPNHLMTLLYHA
1215


EFR95520
774
DQK---AFLE---EKGYYS--P-KV--LTK--IPKYTLYE---CENGRRRMLGS ANEAQKGNQMVLPNHLMTLLYHA
834


WP_003723650
1155
DEE---AFLE---EKGYRH--P-KV--LTK--LPKYTLYE---CEKGRRRMLAS ANEAQKGNQLVLSNHLVSLLYHA
1215


WP_003727705
1155
DEE---AFLE---EKGYHQ--P-KV--LTK--LPKYTLYE---CEKGRRRMLSS ANEAQKGNQLVLSNHLVSLLYHA
1215


WP_003730785
1155
DEE---AFLE---EKGYHQ--P-KV--LTK--LPKYTLYE---CEKGRRRMLSS ANEAQKGNQLVLSNHLVSLLYHA
1215


WP_003733029
1155
DEK---TFLE---EKGYHQ--P-KV--LIK--VPKYTLYE---CKNGRRRMLGS ANEAHKGNQMLLPNHLMALLYHA
1215


WP_003739838
1155
DEK---SFLE---KQGYRQ--P-KV--LTK--LPKYTLYE---CENGRRRMLAS ANEAQKGNQQVLKGQLITLLHHA
1215


WP_014601172
1155
DEE---AFLE---EKGYRH--P-KV--LTK--LPKYTLYE---CEKGRRRMLAS ANEAQKGNQLVLSNHLVSLLYHA
1215


WP_023548323
1155
DEK---VFLE---GKGYHQ--P-KV--LTK--LPKYALYE---CENGRRRMLGS ANEVHKGNQMLLPNHLMTLLYHA
1215


WP_031665337
1155
DEE---AFLE---EKGYRH--P-KV--LTK--LPKYTLYE---CEKGRRRMLAS ANEAQKGNQLVLSNHLVSLLYHA
1215


WP_031669209
1155
DEK---TFLE---EKGYHQ--P-KV--LIK--VPKYTLYE---CENGRRRMLGS ANEAHKGNQMLLPNHLMALLYHA
1215


WP_033920898
1155
DEK---VFLE---GKGYHQ--P-KV--LTK--LPKYALYE---CENGRRRMLGS ANEVHKGNQMLLPNHLMTLLYHA
1215


AKI42028
1158
DEE---AFLE---EKGYRH--P-KV--LTK--LPKYTLYE---CEKGRRRMLAS ANEAQKGNQLVLSNHLVSLLYHA
1218


AKI50529
1158
DEK---VFLE---GKGYHQ--P-KV--LTK--LPKYALYE---CENGRRRMLGS ANEVHKGNQMLLPNHLMTLLYHA
1218


EFR83390
603
DEE---AFLE---EKGYRH--P-KV--LTK--LPKYTLYE---CEKGRRRMLAS ANEAQKGNQLVLSNHLVSLLYHA
663


WP_046323366
1155
DQK---EFLE---GKGYRN--P-KV--ITK--IPKYTLYE---CENGRRRMLGS ANEAQKGNQMVLPNHLMTLLYHA
1215


AKE81011
1193
NPI---DFLE---AKGYKE--V-KKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1255


CUO82355
1154
EQI---EYVE--kEEKLSD--VkIIK---Nn-IPLNQLIEi----DGRQYLLTS --ECVNAMQLVLNEEQCKLIADI
1215


WP_033162887
1155
EQL---SYIAspeHEDLID--VrIVK---E--ILKNQLIEi----DGGLYYVTS --EYVTARQLSLNEQSCKLISEI
1217


AGZ01981
1210
NPI---DFLE---AKGYKE--V-KKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1272


AKA60242
1177
NPI---DFLE---AKGYKE--V-KKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


AK540380
1177
NPI---DFLE---AKGYKE--V-KKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1239


4UN5_B
1181
NPI---DFLE---AKGYKE--V-KKDLIIK--LPKYSLFE---LENGRKRMLAS -GELQKGNELALPSKYVNFLYLA
1243


WP_010922251
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_039695303
1249
HRAD----NFNS-TEYLN--YVSEHKKEFEKVLSCVEDFANLYVDVE--KNLSKIR-A VAD-SM---DNFSIEE--
1308


WP_045635197
1247
KNVH----KLDE-PGHLE--YIQKHRNEFKDLLNLVSEFSQKYVLAD--ANLEKIK-S LYA-DN---EQADIEI--
1306


5AXW_A
979
GELYRVIgVNND1LNRIE---VNMIDITYREYLENMNDKRPPRIIKTiaSKTQSIK-K LYEvKSk--KHPQIIKkg
1056


WP_009880683
924
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
989


WP_010922251
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_011054416
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_011284745
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_011285506
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_011527619
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_012560673
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_014407541
1239
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1304


WP_020905136
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_023080005
1239
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1304


WP_023610282
1239
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1304


WP_030125963
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_030126706
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_031488318
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_032460140
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_032461047
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_032462016
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_032462936
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_032464890
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_033888930
1065
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1130


WP_038431314
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_038432938
1239
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1304


WP_038434062
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


BAQ51233
1151
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1216


KGE60162
415
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
480


KGE60856
178
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
243


WP_002989955
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_003030002
1222
YQIE----KNYE-PEHRE--YVEKHKDEFKELLEYISVFSRKYVLAD--NNLTKIE-M LFS-KN---KDAEVSS--
1281


WP_003065552
1250
QRIN----SENS-TKYLD--YVSAHKKEFEKVLSCVEDFANLYVDVE--KNLSKIR-A VAD-SM---DNFSIEE--
1309


WP_001040076
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDIFQIINDFSKRVILAD--ANLEKIN-R LYQ-DNk--ENIPVDE--
1306


WP_001040078
1249
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1314


WP_001040080
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_001040081
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_001040083
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_001040085
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_001040087
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_001040088
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_001040089
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_001040090
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_001040091
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_001040092
1241
SRYNESKgKPEEiEKKQE--FVNQHISYFDDILQLINDFSKRVILAD--ANLEKIN-K LYS-DNk--DNTPVDE--
1306


WP_001040094
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENIPVDE--
1306


WP_001040095
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENIPVDE--
1306


WP_001040096
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENIPVDE--
1306


WP_001040097
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENIPVDE--
1306


WP_001040098
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENIPVDE--
1306


WP_001040099
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENIPVDE--
1306


WP_001040100
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENIPVDE--
1306


WP_001040104
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_001040105
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_001040106
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_001040107
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_001040108
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_001040109
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_001040110
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_015058523
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYS-DNk--DNTPVDE--
1306


WP_017643650
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENIPVDE--
1306


WP_017647151
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_017648376
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_017649527
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_017771611
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_017771984
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


CFQ25032
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


CFV16040
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


KLJ37842
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


KLJ72361
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


KLL20707
1255
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1320


KLL42645
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_047207273
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_047209694
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENIPVDE--
1306


WP_050198062
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_050201642
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_050204027
1241
SRYNELKgKPEEiEQKQE--FVVQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_050881965
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_050886065
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


AHN30376
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYS-DNk--DNTPVDE--
1306


EA078426
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQLINDFSKRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


CCW42055
1241
SRYNESKgKPEEiEKKQE--FVNQHVSYFDDILQIINDFSNRVILAD--ANLEKIN-K LYQ-DNk--ENISVDE--
1306


WP_003041502
1254
KRIN----NPIN-KDHIE--YVKKHRDDFKELLNYVLEFNEKYVGAT--KNGERLK-E AVA-DF---DSKSNEE--
1313


WP_037593752
1223
YQIE----KNYE-PEHRE--YVEKHKDEFKELLEYISVFSRKYVLAD--NNLTKIE-M LFS-KN---KDAEVSS--
1282


WP_049516684
1223
YRIE----KDYE-PEHRE--YVEKHKDEFKELLEYISVFSRKYVLAD--NNLTKIE-M LFS-KN---KDAEVSS--
1282


GAD46167
1222
YQIE----KNYE-PEHRE--YVEKHKDEFKELLEYISVFSRKYVLAD--NNLTKIE-M LFS-KN---KDAEVSS--
1281


WP_018363470
1254
HRIG----NFNS-AEHLK--YVSEHKKEFEEVLSCVENFANVYVDVE--KNLSKIR-A AAD-SM---DNFSIEE--
1313


WP_003043819
1249
QNISATTgSNNLg-------YIEQHREEFKEIFEKIIDFSEKYILKN--KVNSNLK-S SFD-EQfavSDSIL--1-
1310


WP_006269658
1222
YRIE----KDYE-PEHRE--YVEKHKDEFKELLEYISVFSRKYVLAD--NNLTKIE-M LFS-KN---KDAEVSS--
1281


WP_048800889
1242
HRID----NSDN-SEHLK--YITEHKEEFGKLLSYIENFAKSYVDVD--KNLEKIQ-L AVE-KI---DSFSVKE--
1301


WP_012767106
1246
-HAHKIEsSKE--LEHEA--YILDHYNDLYQLLSYIERFASLYVDVE--KNISKVK-E LFS-NI---ESYSISEi-
1308


WP_014612333
1246
-HAHKIEsSKE--LEHEA--YILDHYNDLYQLLSYIERFASLYVDVE--KNISKVK-E LFS-NI---ESYSISEi-
1308


WP_015017095
1246
-HAHKIEsSKE--LEHEA--YILDHYNDLYQLLSYIERFASLYVDVE--KNISKVK-E LFS-NI---ESYSISEi-
1308


WP_015057649
1246
-HAHKIEsSKE--LEHEA--YILDHYNDLYQLLSYIERFASLYVDVE--KNISKVK-E LFS-NI---ESYSISEi-
1308


WP_048327215
1246
-HAHKIEsSKE--LEHEA--YILDHYNDLYQLLSYIERFASLYVDVE--KNISKVK-E LFS-NI---ESYSISEi-
1308


WP_049519324
1246
-HAHKIEsSKE--LEHEA--YILDHYNDLYQLLSYIERFASLYVDVE--KNISKVK-E LFS-NI---ESYSISEi-
1308


WP_012515931
1220
AHYHELTgSSEDvLRKKY--FVDRHLHYFDDIIQMINDFAERHILAS--SNLEKIN-H TYH-NN---SDLPVNEr-
1285


WP_021320964
1220
AHYHELTgSSEDvLRKKY--FVERHLHYFDDIIQMINDFAERHILAS--SNLEKIN-H TYH-NN---SDLPINEr-
1285


WP_037581760
1220
AHYHELTgSSEDvLRKKY--FVERHLHYFDDIIQMINDFAERHILAS--SNLEKIN-H TYH-NN---SDLPVNEr-
1285


WP_004232481
1252
QHVN----NSHK-PEHLN--YVKQHKDEFKDIFNLIISIARINILKP--KVVDNL--- -IN-EF---TEYGQED--
1308


WP_009854540
1247
HRAD----NFNS-TEYLN--YVSEHKKEFEKVLSCVEDFANLYVDVE--KNLSKIR-A VAD-SM---DNFSIEE--
1306


WP_012962174
1248
HRVN----SFNN-SEHLK--YVSEHKKEFGEVLSCVENFAKSYVDVE--KNLGKIR-A VAD-KI---DTFSIED--
1307


WP_039695303
1249
HRAD----NENS-TEYLN--YVSEHKKEFEKVLSCVEDFANLYVDVE--KNLSKIR-A VAD-SM---DNFSIEE--
1308


WP_014334983
1252
HRID----SFNS-TEHLK--YVSEHKKEFEKVLSCVENFSNLYVDVE--KNLSKVR-A AAE-SM---TNFSLEE--
1311


WP_003099269
1240
SHYTKFTgKEEDrEKKRS--YVESHLYYFDEIMQIIVEYSNRYILAD--SNLIKIQ-N LYK-EKd---NFSIEEq-
1305


AHY15608
1240
SHYTKFTgKEEDrEKKRS--YVESHLYYFXEVKSSF---------------------- ------------------
1273


AHY17476
1240
SHYTKFTgKEEDrEKKRS--YVESHLYXFX---------------------------- ------------------
1267


ESR09100
72
SHYTKFTgKEEDrEKKRS--YVESHLYYFDEIMQIIVEYSNRYILAD--SNLIKIQ-N LYK--Ek--DNFSIEEq-
137


AGM98575
1240
SHYTKFTgKEEDrEKKRS--YVESHLYYFDVRLSQVFRVTNVEF-------------- ------- ----------
1281


ALF27331
1222
KNIH----KVDE-PKHLD--YVKKHKDEFKELLDVVSNFSKKNILAE--SNLEKIE-E LYA-QN---NNKDITE--
1281


WP_018372492
1229
KKVDVLVkSKDD---DYD---LEEHRAEFAELLDCIKKFNDMYILAS--SNMSKIE-E IYQ-KNi---DAPIEE--
1289


WP_045618028
1252
QRIN----KISE-PIHKQ--YVETHQSEFKELLTAIISLSKKYI-QK--PNVESL--- LQQ-AF---DQSDKDIyq
1310


WP_045635197
1247
KNVH----KLDE-PGHLE--YIQKHRNEFKDLLNLVSEFSQKYVLAD--ANLEKIK-S LYA-DN---EQADIEI--
1306


WP_002263549
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002263887
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002264920
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002269043
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002269448
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002271977
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002272766
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002273241
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002275430
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002276448
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002277050
1230
HHL-------DN-DYSNE--YVKNHYQQFDILFNEITSFSKKCKLGK--EHIQKIE-E AYSkER---DSASIEE--
1287


WP_002277364
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002279025
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002279859
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002280230
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002281696
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002282247
1230
HHL-------DN-DYSNE--YVKNHYQQFDILFNEITSFSKKCKLGK--EHIQKIE-E AYSkER---DFASIEE--
1287


WP_002282906
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002283846
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002287255
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002288990
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002289641
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002290427
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002295753
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002296423
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002304487
1236
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1295


WP_002305844
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002307203
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002310390
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_002352408
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_012997688
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_014677909
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_019312892
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_019313659
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_019314093
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_019315370
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_019803776
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_019805234
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_024783594
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_024784288
1230
HHL-------DN-DYSNE--YVKNHYQQFDILFNEITSFSKKCKLGK--EHIQKIE-E AYSkER---DFASIEE--
1287


WP_024784666
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_024784894
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_024786433
1230
HHL-------DN-DYSNE--YVKNHYQQFDILFNEITSFSKKCKLGK--EHIQKIE-E AYSkER---DSASIEE--
1287


WP_049473442
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


WP_049474547
1222
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1281


EMC03581
1215
KNIH----KVDE-PKHLD--YVDKHKDEFKELLDVVSNFSKKYTLAE--GNLEKIK-E LYA-QN---NGEDLKE--
1274


WP_000428612
1250
KNIH----RLDE-PEHLE--YIQKHRNEFKGLLNLVSEFSQKYVLAD--ANLEKIK-N LYA-DN---EQADIEI--
1309


WP_000428613
1248
KNVH----KLDE-PEHLE--YIQKHRNEFKDLLNLVSEFSQKYVLAD--ANLEKIQ-N LYA-DN---EQADIEI--
1307


WP_049523028
1243
KRIQ----KKDE-PEHLE--YIKQHHSEFNDLLNFVSEFSQKYVLAE--SNLEKIK-N LYI-DN---EQTNMEE--
1302


WP_003107102
1209
SRYTSFSgKEEDrEKHRH--FVESHLHYFDEIKDIIADFSRRYILAD--ANLEKIL-T LYN-EKn---QFSIEEq-
1274


WP_054279288
1242
SKRDK--gTQSEnME-----YISNHKEKFIEIFHYIIRYAEKNVIKP--KVIERLN-D TENqKF---NDSDLTE1-
1303


WP_049531101
1252
QRIN----KISE-PIHKQ--YVETHQSEFEELLTTIISLSKKYI-QK--PIVESL--- LQQ-AF---EQADKDIyq
1310


WP_049538452
1252
QRIN----KISE-PIHKQ--YVEAHQNEFKELLTTIISLSKKYI-QK--PNVESL--- LQQ-AF---EQADKDIyq
1310


WP_049549711
1254
QRIN----KFSE-PIHKQ--YVEAHQNEFKELLTIIISLSKKYI-QK--PNVESL--- LHQ-AF---EQADNDIyq
1312


WP_007896501
1246
SRYDKLSsKIESeQQKKL--FVEQHLHYFDEILDIVVKHATCYIKAE--NNLKKII-S LYK-KK---EAYSINEq-
1311


EFR44625
1198
SRYDKLSsKIESeQQKKL--FVEQHLHYFDEILDIVVKHATCYIKAE--NNLKKII-S LYK-KK---EAYSINEq-
1263


WP_002897477
1247
KNLH----KLDE-PEHLE--YIQKHRNEFKDLLNLVSEFSQKYILAE--ANLEKIK-D LYA-DN---EQADIEI--
1306


WP_002906454
1253
QRIN----KISE-PIHKQ--YVEAHQNEFKELLTTIISLSKKYI-QK--PNVELL--- LQQ-AF---DQADKDIyq
1311


WP_009729476
1248
KNVH----KLDE-PGHLE--YIQKHRNEFKDLLNLVSEFSQKYVLAD--ANLEKIK-N LYA-DN---EQADIEI--
1307


CQR24647
1238
QHAN----KEDS----VI--YLEKHRHELSELFHHIIGVSEKTILKP--KVEMTLN-E AFE-KHf--EFDEVSE--
1295


WP_000066813
1252
KNVH----KLDE-PEHLE--YIQKHRYEFKDLLNLVSEFSQKYVLAD--ANLEKIK-N LYA-DN---EQADIEI--
1311


WP_009754323
1248
KNVH----KLDE-PEHLE--YIQKHRYEFKDLLNLVSEFSQKYVLAE--ANLEKIK-S LYV-DN---EQADIEI--
1307


WP_044674937
1241
SNIH----KITE-PIHLN--YVNKNKHEFKELLRHISDFSTRYILAQ--DRLSKIE-E LYD-KN---DGDDISD--
1300


WP_044676715
1243
SNIH----KITE-PIHLN--YVNKNKHEFKELLRHISDFSTRYILAQ--DRLSKIE-E LYD-KN---DGDDISD--
1302


WP_044680361
1243
SNIH----KITE-PIHLN--YVNKNKHEFKELLRHISDFSTRYILAQ--DRLSKIE-E LYD-KN---DGDDISD--
1302


WP_044681799
1241
SNIH----KITE-PIHLN--YVNKNKHEFKELLRHISDFSTRYILAQ--DRLSKIE-E LYD-KN---DGDDISD--
1300


WP_049533112
1254
KRIN----NPIN-KDHIE--YVKKHRDDFKELLNYVLEFNEKYVGAT--KNGERLK-E AVA-DF---DSKSNEE--
1313


WP_029090905
1182
STKQA-----DE-AMFLKyyRLEHLEAVFEEL---IRKQAADYQIFE--KLIKKIEvN FYS----c----TYNEk-
1240


WP_006506696
1212
YNAIYKQ-DYDN1DDILMi-----------QLYIELTNKMKVLYPAY-rGIAEKFE-S YVV----i----SKEEk-
1268


AIT42264
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_034440723
1218
KHYNE-----DE--TSHK--FIVEHKAYFDELLNYIVEFANKYLELE--NSIEKIK-D LYH-----gKGPDVEEke
1276


AKQ21048
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


WP_004636532
1212
NRYDKVK-----fPDSIE--YVHDNLAKFDDLLEYVIDFSNKYINAD--KNVQKIQ-K IYK-EH---GTEDVEL--
1271


WP_002364836
1218
KQCLL----PNQ-SESLA--YVEQHQPEFQEILERVVDFAEVHTLAK--SKVQQIV-K LFE-AN---QTADVKE--
1277


WP_016631044
1169
KQCLL----PNQ-SESLA--YVEQHQPEFQEILERVVDFAEVHTLAK--SKVQQIV-K LFE-AN---QTADVKE--
1228


EM575795
954
QHYDEIAhKESF-----D--YVNDHLSEFREILDQVIDFSNRYTIAA--KNTEKIA-E LFE-QN---QESTVQS--
1013


WP_002373311
1218
KQCLL----PNQ-SESLA--YVEQHQPEFQEILERVVDFAEVHTLAK--SKVQQIV-K LFE-AN---QTADVKE--
1277


WP_002378009
1218
KQCLL----PNQ-SESLA--YVEQHQPEFQEILERVVDFAEVHTLAK--SKVQQIV-K LFE-AN---QTADVKE--
1277


WP_002407324
1218
KQCLL----PNQ-SESLA--YVEQHQPEFQEILERVVDFAEVHTLAK--SKVQQIV-K LFE-AN---QTADVKE--
1277


WP_002413717
1218
KQCLL----PNQ-SESLA--YVEQHQPEFQEILERVVDFAEVHTLAK--SKVQQIV-K LFE-AN---QTADVKE--
1277


WP_010775580
1220
KQCLL----PNQ-SESLA--YVEQHQPEFQEILERVVDFAEVHTLAK--SKVQQIV-K LFE-AN---QTADVKE--
1279


WP_010818269
1218
KQCLL----PNQ-SESLA--YVEQHQPEFQEILERVVDFAEVHTLAK--SKVQQIV-K LFE-AN---QTADVKE--
1277


WP_010824395
1218
KQCLL----PNQ-SESLA--YVEQHQPEFQEILERVVDFAEVHTLAK--SKVQQIV-K LFE-AN---QTADVKE--
1277


WP_016622645
1218
KQCLL----PNQ-SESLA--YVEQHQPEFQEILERVVDFAEVHTLAK--SKVQQIV-K LFE-AN---QTADVKE--
1277


WP_033624816
1218
KQCLL----PNQ-SESLA--YVEQHQPEFQEILERVVDFAEVHTLAK--SKVQQIV-K LFE-AN---QTADVKE--
1277


WP_033625576
1218
KQCLL----PNQ-SESLA--YVEQHQPEFQEILERVVDFAEVHTLAK--SKVQQIV-K LFE-TN---QTADVKE--
1277


WP_033789179
1218
KQCLL----PNQ-SESLA--YVEQHQPEFQEILERVVDFAEVHTLAK--SKVQQIV-K LFE-AN---QTADVKE--
1277


WP_002310644
1220
KQYDEIShKESF-----D--YVNEHHKEFSEVFARVLEFAGKYTLAE--KNIEKLE-K IYK-EN---QTDDLAK--
1279


WP_002312694
1221
KQYDEIShKESF-----D--YVNEHHKEFSEVFARVLEFAGKYTLAE--KNIEKLE-K IYK-EN---QTDDLAK--
1280


WP_002314015
1221
KQYDEIShKESF-----D--YVNEHHKEFSEVFARVLEFAGKYTLAE--KNIEKLE-K IYK-EN---QTDDLAK--
1280


WP_002320716
1221
KQYDEIShKESF-----D--YVNEHHKEFSEVFARVLEFAGKYTLAE--KNIEKLE-K IYK-EN---QTDDLAK--
1280


WP_002330729
1220
KQYDEIShKESF-----D--YVNEHHKEFSEVFARVLEFAGKYTLAE--KNIEKLE-K IYK-EN---QTDDLAK--
1279


WP_002335161
1221
KQYDEIShKESF-----D--YVNEHHKEFSEVFARVLEFAGKYTLAE--KNIEKLE-K IYK-EN---QTDDLAK--
1280


WP_002345439
1221
KQYDEIShKESF-----D--YVNEHHKEFSEVFARVLEFAGKYTLAE--KNIEKLE-K IYK-EN---QTDDLAK--
1280


WP_034867970
1211
QHYDKITyQESF-----D--YVNTHLSDFSAILTEVLAFAEKYTLAD--KNIERIQ-E LYE-EN---KYGETSM--
1270


WP_047937432
1221
KQYDEIShKESF-----D--YVNEHHKEFSEVFARVLEFAGKYTLAE--KNIEKLE-K IYK-EN---QTDDLAK--
1280


WP_010720994
1211
QHYDKITyQESF-----D--YVNTHLSDFSAILTEVLAFAEKYTLAD--KNIERIQ-E LYE-EN---KYGEISM--
1270


WP_010737004
1211
QHYDKITyQESF-----D--YVNTHLSDFSAILTEVLAFAEKYTLAD--KNIERIQ-E LYE-EN---KYGETSM--
1270


WP_034700478
1211
QHYDKITyQESF-----D--YVNTHLSDFSAILTEVLAFAEKYTLAD--KNIERIQ-E LYE-EN---KYGEISM--
1270


WP_007209003
1209
KKIIN--gKNSD---SVS--YIQNNKEKFREIFEYIVDFSSKYISAD--ANLNKIE-K IFE-NNfh----KASEqe
1269


WP_023519017
1205
RHYDEINhKVSF-----D--YVNAHKEGENDIFDFISDEGVRYILAP--QHLEKIK-V AYE-KN---KEVDLKE--
1264


WP_010770040
1216
KQVDE-----DS-GKSEE--YVREHRAEFAEILNYVQAFSETKILAN--KNLQTIL-K LYE-EN---KEADIKE--
1274


WP_048604708
1213
KHCNE-----KP-D-SLK--YVTEHQSGFSEIMAHVKDFAEKYTLVD--KNLEKIL-S LYA-KN---MDSEVKE--
1270


WP_010750235
1214
NHYDEIAyKDSY-----D--YVNEHFSNFQDILDKVIIFAEKYTSAP--QKLNQII-A TYE-KN---QEADRKI--
1273


AII16583
1279
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1344


WP_029073316
1226
YKAMKYK-NYSE1SQEEIm-----------NVYDIFVEKLKLYYPTY-kNIATNFE-N FEN----i----SDEEk-
1282


WP_031589969
1226
YKAMKYK-NYDN1DSEKIi-----------DLYRLLINKMELYYPEYrkQLVKKFE-D LKV----i----SIEEk-
1283


KDA45870
1200
NAKDG--------EQKLE-----DHKAEFKELFDKIMEFADKYVVAP--KNSEKIR-R LYE-ENq-----DATPme
1253


WP_039099354
1242
LPLTQ-----SEeLAEQV----------YDEILDQVMHYFPLYDTNQfrAKLSAGKaA DGN-KMv-----QVGQqv
1306


AKP02966
1238
QIPDE------DpDQILAf----YDKNILVEILQELITKMKKFYPFY--KNEQEFLaS FNQ--------ATTSEk-
1296


WP_010991369
1216
ANCEV-----SD-GKSLD--YIESNREMFAELLAHVSEFAKRYTLAE--ANLNKIN-Q LFE-QN---KEGDIKA--
1274


WP_033838504
1216
ANCEV-----SD-GKSLD--YIESNREMFAELLAHVSEFAKRYTLAE--ANLNKIN-Q LFE-QN---KEGDIKA--
1274


EHN60060
1219
ANCEV-----SD-GKSLD--YIESNREMFAELLAHVSEFAKRYTLAE--ANLNKIN-Q LFE-QN---KEGDIKA--
1277


EFR89594
985
ANCEV-----SD-GKSLD--YIESNREMFAELLAHVSEFAKRYTLAE--ANLNKIN-Q LFE-QN---KEGDIKA--
1043


WP_038409211
1216
KNCEA-----ND-GESLA--YIEMHREMFAELLAYISEFAKRYTLAN--DRLEKIN-M FFE-QN---KKGDIKV--
1274


EFR95520
835
KNCEA-----ND-GESLA--YIEMHREMFAELLAYISEFAKRYTLAN--DRLEKIN-M FFE-QN---KKGDIKV--
893


WP_003723650
1216
KNCEA-----SD-GKSLK--YIEAHRETFSELLAQVSEFATRYTLAD--ANLSKIN-N LFE-QN---KEGDIKA--
1274


WP_003727705
1216
KNCEA-----SD-GKSLK--YIEAHRETFSELLAQVSEFATKYTLAD--ANLSKIN-N LFE-QN---KEGDIKA--
1274


WP_003730785
1216
KNCEA-----SD-GKSLK--YIEAHRETFSELLAQVSEFATKYTLAD--ANLSKIN-N LFE-QN---KEGDIKA--
1274


WP_003733029
1216
EKYEA-----ID-GESLA--YIEVHRALFDELLAYISEFARKYTLSN--DRLDEIN-M LYE-RN---KDGDVKS--
1274


WP_003739838
1216
KNCEA-----SD-GKSLD--YIESNREMFGELLAHVSEFAKRYTLAD--ANLSKIN-Q LFE-QN---KDNDIKV--
1274


WP_014601172
1216
KNCEA-----SD-GKSLK--YIEAHRETFSELLAQVSEFATRYTLAD--ANLSKIN-N LFE-QN---KEGDIQA--
1274


WP_023548323
1216
EKREA-----ID-GESLA--YIEAHKAVFGELLAHISEFARKYTLAN--DKLDEIN-M LYE-RN---KDGDVKS--
1274


WP_031665337
1216
KNCEA-----SD-GKSLK--YIEAHRETFSELLAQVSEFATRYTLAD--ANLSKIN-N LFE-QN---KEGDIKA--
1274


WP_031669209
1216
EKYEA-----ID-GESLA--YIEVHRALFDELLAYISEFARKYTLSN--DRLDEIN-M LYE-RN---KDGDVKS--
1274


WP_033920898
1216
EKREA-----ID-GESLA--YIEAHKAVFGELLAHISEFARKYTLAN--DKLDEIN-M LYE-RN---KDGDVKS--
1274


AKI42028
1219
KNCEA-----SD-GKSLK--YIEAHRETFSELLAQVSEFATRYTLAD--ANLSKIN-N LFE-QN---KEGDIQA--
1277


AKI50529
1219
EKREA-----ID-GESLA--YIEAHKAVFGELLAHISEFARKYTLAN--DKLDEIN-M LYE-RN---KDGDVKS--
1277


EFR83390
664
KNCEA-----SD-GKSLK--YTEAHRETFSELLAQVSEFATRYTLAD--ANLSKIN-N LFE-QN---KEGDIKX--
722


WP_046323366
1216
KNCEA-----SD-GKSLA--YIESHREMFAELLDSISEFASRYTLAD--ANLEKIN-T IFE-QN---KSGDVKV--
1274


AKE81011
1256
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1321


CUO82355
1216
YNAIYKQ-DFDG1DNMLMi-----------QLYLQLIDKLKTLYPIY-mGIVEKFE-K FVS----i----SKEEk-
1272


WP_033162887
1218
YAAMLKK-RYEY1DEEEIf-----------DLYLQLLQKMDTLYPAY-kGIAKRFF-D FKN----i----DVVEk-
1274


AGZ01981
1273
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1338


AKA60242
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


AK540380
1240
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1305


4UN5_B
1244
SHYEKLKgSPEDnEQKQL--FVEQHKHYLDEIIEQISEFSKRVILAD--ANLDKVL-S AYN-KH---RDKPIREq-
1309


WP_010922251
1306
-AE---NII HLFTLTNLGAP-AAFKYFD--custom character TI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1365


WP_039695303
1309
ISN---SFI NLLTLTALGAP-ADFNFLG--EKI--PRK--R-YTSTKECL NATLIHQSITGLYETRIDLSKL--
1369


WP_045635197
1307
LAN---SFI NLLTFTALGAP-AAFKFFG--KDI--DRK--R-YTTVSEIL NATLIHQSITGLYETWIDLSKL--
1367


5AXW_A

--------- ----------------------------------------- ------------------------



WP_009880683
990
-AE---NII HLFTLTNLGAP-AAFKCFD--TTI--GRN--R-YKSIKEVL DATLIHQSITGLYETRIDLSQL--
1049


WP_010922251
1306
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1365


WP_011054416
1306
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1365


WP_011284745
1306
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATFIHQSITGLYETRIDLSQL--
1365


WP_011285506
1306
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1365


WP_011527619
1306
-AE---NII HLFTLTNLGAP-TAFKYFD--TTI--DRK--R-YTSTKEVL DATFIHQSITGLYETRIDLSQL--
1365


WP_012560673
1306
-AE---NII HLFTLTNLGAP-AAFKCFD--TTI--GRN--R-YKSIKEVL DATLIHQSITGLYETRIDLSQL--
1365


WP_014407541
1305
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1364


WP_020905136
1306
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1365


WP_023080005
1305
-AK---NII HLFTLTNLGAP-AAFKYFD--TTI--ERN--R-YKSIKEVL DATLIHQSITGLYETRIDLSQL--
1364


WP_023610282
1305
-AK---NII HLFTLTNLGAP-AAFKYFD--TTI--ERN--R-YKSIKEVL DATLIHQSITGLYEIRIDLSQL--
1364


WP_030125963
1306
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--GRN--R-YKSIKEVL DATLIHQSITGLYETRIDLSQL--
1365


WP_030126706
1306
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1365


WP_031488318
1306
-AE---NII HLFTLTNFGAP-AAFIYFD--TTI--GRN--R-YKSIKEVL DATLIHQSITGLYETRIDLSQL--
1365


WP_032460140
1306
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--GRN--R-YKSIKEVL DATLIHQSITGLYETRIDLSQL--
1365


WP_032461047
1306
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--GRN--R-YKSIKEVL DATLIHQSITGLYETRIDLSQL--
1365


WP_032462016
1306
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1365


WP_032462936
1306
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1365


WP_032464890
1306
-AE---NII HLFTLTNLGAP-TAFKYFD--TTI--DRK--R-YTSTKEVL DATFIHQSITGLYETRIDLSQL--
1365


WP_033888930
1131
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1190


WP_038431314
1306
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1365


WP_038432938
1305
-AK---NII HLFTLTNLGAP-AAFKYFD--TTI--ERN--R-YKSIKEVL DATLIHQSITGLYETRIDLSQL--
1364


WP_038434062
1306
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--GRN--R-YKSIKEVL DATLIHQSITGLYETRIDLSQL--
1365


BAQ51233
1217
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1276


KGE60162
481
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
540


KGE60856
244
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
303


WP_002989955
1306
-AE---NII HLFTLTNLGAP-TAFKYFD--TTI--DRK--R-YTSTKEVL DATFIHQSITGLYETRIDLSQL--
1365


WP_003030002
1282
LAK---SFI SLLTFTAFGAP-AAFNFFG--ENI--DRK--R-YTSVTECL NATLIHQSITGLYETRIDLSKL--
1342


WP_003065552
1310
ISN---SFI NLLTLTALGAP-ADFNFLG--EKI--PRK--R-YTSTKECL NATLIHQSITGLYETRIDLSKI--
1370


WP_001040076
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040078
1315
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLSKL--
1375


WP_001040080
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040081
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040083
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040085
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040087
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040088
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040089
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040090
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040091
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040092
1307
LAK---NII NLFTFTSLGAP-AAFKFFD--KSV--DRK--R-YTSTKEVL DSTLIHQSITGLYETRIDLGKL--
1367


WP_001040094
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040095
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040096
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040097
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040098
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040099
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHKSITGLYETRIDLGKL--
1367


WP_001040100
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040104
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040105
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040106
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040107
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040108
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_001040109
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQFITGLYETRIDLGKL--
1367


WP_001040110
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_015058523
1307
LAK---NII NLFTFTSLGAP-AAFKFFD--KSV--DRK--R-YTSTKEVL DSTLIHQSITGLYETRIDLGKL--
1367


WP_017643650
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_017647151
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_017648376
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_017649527
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_017771611
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_017771984
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


CFQ25032
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


CFV16040
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


KLJ37842
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


KLJ72361
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


KLL20707
1321
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1381


KLL42645
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_047207273
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_047209694
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHKSITGLYETRIDLGKL--
1367


WP_050198062
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_050201642
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_050204027
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_050881965
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KII--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_050886065
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


AHN30376
1307
LAK---NII NLFTFTSLGAP-AAFKFFD--KSV--DRK--R-YTSTKEVL DSTLIHQSITGLYETRIDLGKL--
1367


EA078426
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


CCW42055
1307
LAN---NII NLFTFTSLGAP-AAFKFFD--KIV--DRK--R-YTSTKEVL NSTLIHQSITGLYETRIDLGKL--
1367


WP_003041502
1314
ICT---SFL GLFELTSLGSA-SDFEFLG--VKI--PRY--RdYTPSSLLK DSTLIHQSITGLYETRIDLSKL--
1383


WP_037593752
1283
LAK---SFI SLLTFTAFGAP-AAFNFFG--ENI--DRK--R-YTSVTECL NATLIHQSITGLYETRIDLSKL--
1343


WP_049516684
1283
LAK---SFI SLLTFTAFGAP-AAFNFFG--ENI--DRK--R-YTSVTECL NATLIHQSITGLYETRIDLSKL--
1343


GAD46167
1282
LAK---SFI SLLTFTAFGAP-AAFNFFG--ENI--DRK--R-YTSVTECL NATLIHQSITGLYETRIDLSKL--
1342


WP_018363470
1314
ISD---SFI NLLTLTALGAP-ADFNFLG--EKI--PRK--R-YNSTKECL NATLIHQSITGLYETRIDLSKL--
1374


WP_003043819
1311
-SN---SFV SLLKYTSFGAS-GGFTFLD--LDVkqGRL--R-YQTVTEVL DATLIYQSITGLYETRTDLSQL--
1372


WP_006269658
1282
LAK---SFI SLLTFTAFGAP-AAFNFFG--ENI--DRK--R-YTSVTECL NATLIHQSITGLYETRIDLSKL--
1342


WP_048800889
1302
ISN---SFI HLLTLTALGAP-ADFNFLG--EKI--PRK--R-YTSTKECL NATLIHQSITGLYETQTDLSKL--
1362


WP_012767106
1309
-CS---SVI NLLTLTASGAP-ADFKFLG--TTI--PRK--R-YGSPQSIL SSTLIHQSITGLYETRIDLSQL--
1368


WP_014612333
1309
-CS---SVI NLLTLTASGAP-ADFKFLG--TTI--PRK--R-YGSPQSIL SSTLIHQSITGLYETRIDLSQL--
1368


WP_015017095
1309
-CS---SVI NLLTLTASGAP-ADFKFLG--TTI--PRK--R-YGSPQSIL SSTLIHQSITGLYETRIDLSQL--
1368


WP_015057649
1309
-CS---SVI NLLTLTASGAP-ADFKFLG--TTI--PRK--R-YGSPQSIL SSTLIHQSITGLYETRIDLSQL--
1368


WP_048327215
1309
-CS---SVI NLLTLTASGAP-ADFKFLG--TTI--PRK--R-YGSPQSIL SSTLIHQSITGLYETRIDLSQL--
1368


WP_049519324
1309
-CS---SVI NLLTLTASGAP-ADFKFLG--TTI--PRK--R-YGSPQSIL SSTLIHQSITGLYETRIDLSQL--
1368


WP_012515931
1286
-AE---NII NVFTFVALGAP-AAFKFFD--ATI--DRK--R-YTSTKEVL NATLIHQSVTGLYETRIDLSQL--
1345


WP_021320964
1286
-AE---NII NVFTFVALGAP-AAFKFFD--ATI--DRK--R-YTSTKEVL NATLIHQSVTGLYETRIDLSQL--
1345


WP_037581760
1286
-AE---NII NVFTFVALGAP-AAFKFFD--ATI--DRK--R-YTSTKEVL NATLIHQSVTGLYETRIDLSQL--
1345


WP_004232481
1309
ISS1seSFI NLLKFISFGAP-GAFKFLK--LDV--KQSn1R-YKSTTEAL SATLIHQSVTGLYETRIDLSKL--
1374


WP_009854540
1307
ISN---SFI NLLTLTALGAP-ADFNFLG--EKI--PRK--R-YTSTKECL TATLIHQSITGLYETRIDLSKL--
1367


WP_012962174
1308
ISI---SFV NLLTLTALGAP-ADFNFLG--EKI--PRK--R-YTSTKECL NATLIHQSITGLYETRIDLSKL--
1368


WP_039695303
1309
ISN---SFI NLLTLTALGAP-ADFNFLG--EKI--PRK--R-YTSTKECL NATLIHQSITGLYETRIDLSKL--
1369


WP_014334983
1312
ISA---SFI NLLTLTALGAP-ADFNFLG--EKI--PRK--R-YTSTKECL SATLIHQSVTGLYETRIDLSKL--
1372


WP_003099269
1306
-AI---NML NLFTFTDLGAP-SAFKFFN--GDI--DRK--R-YSSTNEII NSTLIYQSPTGLYETRIDLSKL--
1365


AHY15608

--------- ----------------------------------------- ------------------------



AHY17476

--------- ----------------------------------------- ------------------------



ESR09100
138
-AI---NML NLFTFTDLGAP-SAFKFFNg--DI--DRK--R-YSSTNEII NSTLIYQSPTGLYETRIDLSKL--
197


AGM98575

--------- ----------------------------------------- ------------------------



ALF27331
1282
LAS---SFI NLLTFTAIGAP-AAFKFFD--NNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSRL--
1342


WP_018372492
1290
VAR---SFV -LLNFTMMGAA-TDFKFFG--QII--PRK--R-YPSTTECL KSTLIHQSVTGLYETRIDLSKL--
1350


WP_045618028
1311
LSE---SFI SLLKLISFGAP-GTFKFLG--VEI--SQSnvR-YQSVSSCF NATLIHQSITGLYETRIDLSKL--
1373


WP_045635197
1307
LAN---SFI NLLTFTALGAP-AAFKFFG--KDI--DRK--R-YTTVSEIL NATLIHQSITGLYETWIDLSKL--
1367


WP_002263549
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLNKL--
1342


WP_002263887
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLNKL--
1342


WP_002264920
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002269043
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLNKL--
1342


WP_002269448
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002271977
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002272766
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002273241
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002275430
1282
LSS---SFI NLLTFTAIGAP-AAFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002276448
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002277050
1288
LAD---GFI KLLGFTQLGAT-SPFSFLG--IKL--NQK--Q-YTGKKDYL EATLIHQSITGLYETRIDLNKL--
1352


WP_002277364
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002279025
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002279859
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002280230
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002281696
1282
LSS---SFI NLLTFTAIGAP-AAFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002282247
1288
LAD---GFI KLLGFTQLGAT-SPFSFLG--IKL--NQK--Q-YTGKKDYL EATLIHQSITGLYETRIDLSKL--
1352


WP_002282906
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002283846
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002287255
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002288990
1282
LAS---SFI NLLTFTAIGAP-AAFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002289641
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002290427
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002295753
1282
LAS---SFI NLLTFTAIGAP-AAFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002296423
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002304487
1296
LAS---SFI NLLTFTAIGAP-AAFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLNKL--
1356


WP_002305844
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002307203
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002310390
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_002352408
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_012997688
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_014677909
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_019312892
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_019313659
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLNKL--
1342


WP_019314093
1282
LAS---SFI NLLTFTAIGAP-AAFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_019315370
1282
LSS---SFI NLLTFTAIGAP-AAFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_019803776
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLNKL--
1342


WP_019805234
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_024783594
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLNKL--
1342


WP_024784288
1288
LAD---GFI KLLGFTQLGAT-SPFSFLG--IKL--NQK--Q-YTGKKDYL EATLIHQSITGLYETRIDLSKL--
1352


WP_024784666
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_024784894
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_024786433
1288
LAD---GFI KLLGFTQLGAT-SPFSFLG--IKL--NQK--Q-YTGKKDYL EATLIHQSITGLYETRIDLSKL--
1352


WP_049473442
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1342


WP_049474547
1282
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL KATLIHQSITGLYETRIDLSKL--
1342


EMC03581
1275
LAS---SFI NLLTFTAIGAP-ATFKFFD--KNI--DRK--R-YTSTTEIL NATLIHQSITGLYETRIDLSKL--
1335


WP_000428612
1310
LAN---SFI NLLTFTALGAP-AAFKFFG--KDV--DRK--R-YTTVSEIL NATLIHQSITGLYETRIDLSKL--
1370


WP_000428613
1308
LAN---SFI NLLTFTALGAP-AAFKFFG--KDI--DRK--R-YTTVSEIL NATLIHQSITGLYETRIDLSKL--
1368


WP_049523028
1303
IAN---SFI NLLTFTAFGAP-AVFKFFG--KDI--ERK--R-YSTVTEIL KATLIHQSLTGLYETRIDLSKL--
1363


WP_003107102
1275
-AT---NML NLFTFTGLGAP-ATLKFFN--VDI--DRK--R-YTSSTEIL NSTLIRQSITGLYETRIDLSKI--
1334


WP_054279288
1304
-SI---SFL NLFKFTSFGAP-EKFTFLN--SEIkqDDV--R-YRSTKECL NSTLIHQSVTGLYETRIDLSQF--
1365


WP_049531101
1311
LSE---SFI SLLKLTSFGAP-GAFRFLG--VEI--SQSnvR-YQSVSSCF NATLIHQSITGLYETRIDLSKL--
1373


WP_049538452
1311
LSE---SFI SLLKLTSFGAP-GAFKFLG--VEI--SQSsvR-YKPNSQFL DATLIHQSITGLYETRIDLSKL--
1373


WP_049549711
1313
LSE---SFI SLLKLTSFGAP-GAFKFLG--AEI--SQSsvR-YKPNSQFL DTTLIHQSITGLYETRIDLSKL--
1375


WP_007896501
1312
-AL---NML NLFIFTSLGAP-STFVFFD--ETI--DRK--R-YTTSSDVL NGILIQQSITGLYETRIDLSRF--
1371


EFR44625
1264
-AL---NML NLFIFTSLGAP-STFVFFD--ETI--DRK--R-YTTSSDVL NGILIQQSITGLYETRIDLSRF--
1323


WP_002897477
1307
LAN---SFI NLLTFTALGAP-AAFKFFG--KDV--DRK--R-YTTVSEIL NATLIHQSITGLYETRIDLSKL--
1367


WP_002906454
1312
LSE---SFI SLLKLTSFGAP-GAFKFLG--VEI--SQSsvR-YKPNSQFL DTTLIHQSITGLYETRIDLSKL--
1374


WP_009729476
1308
LAN---SFI NLLTFTALGAP-AAFKFFG--KDV--DRK--R-YTTVSEIL NATLIHQSITGLYETRIDLSKL--
1368


CQR24647
1296
LAQ---SFI SLLKFTAFGAP-GGFKFLD--ADI--KQSn1R-YQTVTEVL SSTLIHQSVTGLYETRIDLSKL--
1358


WP_000066813
1312
LAN---SFI NLLTFTALGAP-AAFKFLG--KDV--DRK--R-YTTVSEIL NATLIHQSITGLYETRIDLSKL--
1372


WP_009754323
1308
LAN---SFI NLLTFTALGAP-AAFKFFG--KDV--DRK--R-YTTVSEIL NATLIHQSITGLYETRIDLSKL--
1368


WP_044674937
1301
LTS---SFV NLLTFTAIGAP-AAFKFLG--SVI--DRK--R-YTSIAEIL EATLIHQSVTGLYETRIDLSKL--
1361


WP_044676715
1303
LTS---SFV NLLTFTAIGAP-AAFKFLG--SVI--DRK--R-YTSIAEIL EATLIHQSVTGLYETRIDLSKL--
1363


WP_044680361
1303
LTS---SFV NLLTFTAIGAP-AAFKFLG--SVI--DRK--R-YTSIAEIL EATLIHQSVTGLYETRIDLSKL--
1363


WP_044681799
1301
LTS---SFV NLLTFTAIGAP-AAFKFLG--SVI--DRK--R-YTSIAEIL EATLIHQSVTGLYETRIDLSKL--
1361


WP_049533112
1314
ICT---SFL GLFELTSLGSA-SDFEFLG--VKI--PRY--RdYTPSSLLK DSTLIHQSITGLYETRIDLSKL--
1383


WP_029090905
1241
-VK----VI ELLKITQANATnGDLKLLK----M-sNREg-R-LGSVSVAL DFKIINQSVTGLYQSIEDYNN---
1300


WP_006506696
1269
-AN----II QMLIVMHRGPQnGNIVYDDf--KI-sDRIg-R-LKTKNHNL NIVFISQSPTGIYTKKYKL-----
1329


AIT42264
1306
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1365


WP_034440723
1277
LVE---SFI NLLAITKCGPA-ADITFLG--EKI--SRK--R-YRSTNCLW GSEVIFQSPTGLYETRLRLE----
1335


AKQ21048
1306
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1365


WP_004636532
1272
TVE---SFV NLMTFTAMGAP-ATFKFYG--ESI--TRS--R-YTSITEFR GSTLIFQSITGLYETRYKL-----
1329


WP_002364836
1278
IAA---SFI QLMQFNAMGAP-STFKFFQ--KDI--ERA--R-YTSIKEIF DATIIYQSTTGLYETRRKV-----
1335


WP_016631044
1229
IAA---SFI QLMQFNAMGAP-STFKFFQ--KDI--ERA--R-YTSIKEIF DATIIYQSPTGLYETRRKV-----
1286


EM575795
1014
LSQ---SFI NLMQLNAMGAP-ADFKFFD--VII--PRK--R-YPSLTEIW ESTITYQSITGLRETRTRMATLwd
1076


WP_002373311
1278
IAA---SFI QLMQFNAMGAP-STFKFFQ--KDI--ERA--R-YTSIKEIF DATIIYQSTTGLYETRRKV-----
1335


WP_002378009
1278
IAA---SFI QLMQFNAMGAP-STFKFFQ--KDI--ERA--R-YTSIKEIF DATIIYQSTTGLYETRRKV-----
1335


WP_002407324
1278
IAA---SFI QLMQFNAMGAP-STFKFFQ--KDI--ERA--R-YTSIKEIF DATIIYQSTTGLYETRRKV-----
1335


WP_002413717
1278
IAA---SFI QLMQFNAMGAP-STFKFFQ--KDI--ERA--R-YTSIKEIF DATIIYQSTTGLYETRRKV-----
1335


WP_010775580
1280
IAA---SFI QLMQFNAMGAP-STFKFFQ--KDI--ERA--R-YTSIKEIF DATIIYQSTTGLYETRRKV-----
1337


WP_010818269
1278
IAA---SFI QLMQFNAMGAP-STFKFFQ--KDI--ERA--R-YTSIKEIF DATIIYQSTTGLYETRRKV-----
1335


WP_010824395
1278
IAA---SFI QLMQFNAMGAP-STFKFFQ--KDI--ERA--R-YTSIKEIF DATIIYQSTTGLYETRRKV-----
1335


WP_016622645
1278
IAA---SFI QLMQFNAMGAP-STFKFFQ--KDI--ERA--R-YTSIKEIF DATIIYQSTTGLYETRRKV-----
1335


WP_033624816
1278
IAA---SFI QLMQFNAMGAP-STFKFFQ--KDI--ERA--R-YTSIKEIF DATIIYQSTTGLYETRRKV-----
1335


WP_033625576
1278
IAA---SFI QLMQFNAMGAP-STFKFFQ--KDI--ERA--R-YTSIKEIF DATIIYQSTTGLYETRRKV-----
1335


WP_033789179
1278
IAA---SFI QLMQFNAMGAP-STFKFFQ--KDI--ERA--R-YTSIKEIF DATIIYQSTTGLYETRRKV-----
1335


WP_002310644
1280
LAS---SFV NLMQFNAMGAP-ADFKFFD--VTI--PRK--R-YTSLTEIW QSTIIHQSITGLYETRIRMGK---
1339


WP_002312694
1281
LAS---SFV NLMQFNAMGAP-ADFKFFD--VTI--PRK--R-YTSLTEIW QSTIIHQSITGLYETRIRMGK---
1340


WP_002314015
1281
LAS---SFV NLMQFNAMGAP-ADFKFFD--VTI--PRK--R-YTSLTEIW QSTIIHQSITGLYETRIRMGK---
1340


WP_002320716
1281
LAS---SFV NLMQFNAMGAP-ADFKFFD--VTI--PRK--R-YTSLTEIW QSTIIHQSITGLYETRIRMGK---
1340


WP_002330729
1280
LAS---SFV NLMQFNAMGAP-ADFKFFD--VTI--PRK--R-YTSLTEIW QSTIIHQSITGLYETRIRMGK---
1339


WP_002335161
1281
LAS---SFV NLMQFNAMGAP-ADFKFFD--VTI--PRK--R-YTSLTEIW QSTIIHQSITGLYETRIRMGK---
1340


WP_002345439
1281
LAS---SFV NLMQFNAMGAP-ADFKFFD--VTI--PRK--R-YTSLTEIW QSTIIHQSITGLYETRIRMGK---
1340


WP_034867970
1271
IAQ---SFL QLLQFNAIGAP-ADFKFFG--VTI--PRK--R-YTSLTEIW DATIIYQSVTGLYETRIRMGDLwa
1333


WP_047937432
1281
LAS---SFV NLMQFNAMGAP-ADFKFFD--VTI--PRK--R-YTSLTEIW QSTIIHQSITGLYETRIRMGK---
1340


WP_010720994
1271
IAQ---SFL QLLQFNAIGAP-ADFKFFG--VTI--PRK--R-YTSLTEIW DATIIYQSVTGLYETRIRMGDLwa
1333


WP_010737004
1271
IAQ---SFL QLLQFNAIGAP-ADFKFFG--VTI--PRK--R-YTSLTEIW DATIIYQSVTGLYETRIRMGDLwa
1333


WP_034700478
1271
IAQ---SFL QLLQFNAIGAP-ADFKFFG--VTI--PRK--R-YTSLTEIW DATIIYQSVTGLYETRIRMGDLwa
1333


WP_007209003
1270
IAK---SFI NLLTFTAMGAP-ADFEFFG--EKI--PRK--R-YVSISEII DAVFIHQSITGLYETRVRLTEV--
1330


WP_023519017
1265
MID---AIL SLLKFTLFGAS-VEFKFFD--IKI---LK--R-YKSLTDIW EATIIYQSVTGLYERRVEVRKLwd
1326


WP_010770040
1275
IAE---SFV NLMKFSAYGAP-MDFKFFG--KTI--PRS--R-YTSVGELL SATIINQSITGLYETRRKL-----
1332


WP_048604708
1271
IAQ---SFV DLMQLNAFGAP-ADFKFFG--ETI--PRK--R-YTSVNELL EATIINQSITGLYETRRRL-----
1328


WP_010750235
1274
MAH---SFV NLMQFNALGAP-ADFKFFD--TTI--TRK--R-YTSLTEIW QSTIIYQSVTGLYETRRRMADLwd
1336


AII16583
1345
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1404


WP_029073316
1283
-CE----VI QMLVVMHAGPQnGNITFDDf--KL-sNRLg-R-LNCKTISL TTVFIADSPTGMYSKKYKL-----
1343


WP_031589969
1284
-CN----II QILATLHCNSSiGKIMYSDf--KI-sTTIg-R-LNGRTISL DISFIAESPTGMYSKKYKL-----
1344


KDA45870
1254
LGK---NFV ELLRYTADGAA-SDFKFFG--ENI--PRK--R-YNSAGSLL NGTLIYQSKTGLYETRIDLGKL--
1314


WP_039099354
1307
ILDr----V -LIGLHANAAV-SDLGVLKisTPL--GKM--Q---QPSGIS DTQIIYQSPTGLFERRVALRDL--
1368


AKP02966
1297
INS1-eELI TLLHANSTSAH-LIFNNIE-kKAF--GRK-------THGLT DTDFIYQSVTGLYETRIHIE----
1356


WP_010991369
1275
IAQ---SFV DLMAFNAMGAP-ASFKFFE--TTI--ERK--R-YNNLKELL NSTIIYQSITGLYESRKRL-----
1332


WP_033838504
1275
IAQ---SFV DLMAFNAMGAP-ASFKFFE--TTI--ERK--R-YNNLKELL NSTIIYQSITGLYESRKRL-----
1332


EHN60060
1278
IAQ---SFV DLMAFNAMGAP-ASFKFFE--TTI--ERK--R-YNNLKELL NSTIIYQSITGLYESRKRL-----
1335


EFR89594
1044
IAQ---SFV DLMAFNAMGAP-ASFKFFE--TTI--ERK--R-YNNLKELL NSTIIYQSITGLYESRKRL-----
1101


WP_038409211
1275
IAK---SFD KLKVFNAFGAP-RDFEFFE--TTI--KRK--R-YYNIKELL NATIIYQSITGLYEARKRL-----
1332


EFR95520
894
IAK---SFD KLKVFNAFGAP-RDFEFFE--TTI--KRK--R-YYNIKELL NATIIYQSITGLYEARKRL-----
951


WP_003723650
1275
IAQ---SFV DLMAFNAMGAP-ASFKFFE--ATI--DRK--R-YTNLKELL SSTIIYQSITGLYESRKRL-----
1332


WP_003727705
1275
IAQ---SFV DLMAFNAMGAP-ASFKFFE--ATI--DRK--R-YTNLKELL SSTIIYQSITGLYESRKRL-----
1332


WP_003730785
1275
IAQ---SFV DLMAFNAMGAP-ASFKFFE--ATI--DRK--R-YTNLKELL SSTIIYQSITGLYESRKRL-----
1332


WP_003733029
1275
IAE---SFV SLKKFNAFGVH-QDFSFFG--TKI--ERK--R-DRKLNELL NSTIIYQSITGLYESRKRL-----
1332


WP_003739838
1275
IAQ---SFV NLMAFNAMGAP-ASFKFFE--ATI--ERK--R-YTNLKELL SATIIYQSITGLYEARKRL-----
1332


WP_014601172
1275
IAQ---SFV DLMAFNAMGAP-ASFKFFE--ATI--DRK--R-YTNLKELL SSTIIYQSITGLYESRKRL-----
1332


WP_023548323
1275
IAE---SFV SLKKFNAFGVH-KDFNFFG--TTI--KRK--R-DRKLKELL NSTIIYQSITGLYESRKRL-----
1332


WP_031665337
1275
IAQ---SFV DLMAFNAMGAP-ASFKFFE--ATI--DRK--R-YTNLKELL SSTIIYQSITGLYESRKRL-----
1332


WP_031669209
1275
IAE---SFV SLKKFNAFGVH-QDFSFFG--TKI--ERK--R-DRKLNELL NSTIIYQSITGLYESRKRL-----
1332


WP_033920898
1275
IAE---SFV SLKKFNAFGVH-KDFNFFG--TTI--KRK--R-DRKLKELL NSTIIYQSITGLYESRKRL-----
1332


AKI42028
1278
IAQ---SFV DLMAFNAMGAP-ASFKFFE--ATI--DRK--R-YTNLKELL SSTIIYQSITGLYESRKRL-----
1335


AKI50529
1278
IAE---SFV SLKKFNAFGVH-KDFNFFG--TTI--KRK--R-DRKLKELL NSTIIYQSITGLYESRKRL-----
1335


EFR83390
723
IAQ---SFV DLMVFNAMGAP-ASFKFFE--ATI--DRK--R-YTNLKELL SSTIIYQSITGLYESRKRL-----
780


WP_046323366
1275
IAQ---SFV NLLEFNAMGAP-ASFKYFE--TNI--ERK--R-YNNLKELL NATIIYQSITGLYEARKRL-----
1332


AKE81011
1322
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1381


CUO82355
1273
-AN----VI QMLIIMHKGPQnGNIIYDDf--NV-gKRIg-R-LNGRTFYL NIEFISQSPTGIYTKKYKL-----
1333


WP_033162887
1275
-CD----VI QILIIMHAGPMnGNIMYDDf--KF-tNRIg-R-FTHKNIDL KTTFISTSVTGLFSKKYKL-----
1335


AGZ01981
1339
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1398


AKA60242
1306
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1365


AKS40380
1306
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1365


4UN5_B
1310
-AE---NII HLFTLTNLGAP-AAFKYFD--TTI--DRK--R-YTSTKEVL DATLIHQSITGLYETRIDLSQL--
1369














WP_010922251
1366
GGD
1368



WP_039695303
1370
GEE
1372



WP_045635197
1368
GED
1370



5AXW_A

---




WP_009880683
1050
GGD
1052



WP_010922251
1366
GGD
1368



WP_011054416
1366
GGD
1368



WP_011284745
1366
GGD
1368



WP_011285506
1366
GGD
1368



WP_011527619
1366
GGD
1368



WP_012560673
1366
GGD
1368



WP_014407541
1365
GGD
1367



WP_020905136
1366
GGD
1368



WP_023080005
1365
GGD
1367



WP_023610282
1365
GGD
1367



WP_030125963
1366
GGD
1368



WP_030126706
1366
GGD
1368



WP_031488318
1366
GGD
1368



WP_032460140
1366
GGD
1368



WP_032461047
1366
GGD
1368



WP_032462016
1366
GGD
1368



WP_032462936
1366
GGD
1368



WP_032464890
1366
GGD
1368



WP_033888930
1191
GGD
1193



WP_038431314
1366
GGD
1368



WP_038432938
1365
GGD
1367



WP_038434062
1366
GGD
1368



BAQ51233
1277
GGD
1279



KGE60162
541
GGD
543



KGE60856
304
GGD
306



WP_002989955
1366
GGD
1368



WP_003030002
1343
GED
1345



WP_003065552
1371
GEE
1373



WP_001040076
1368
GED
1370



WP_001040078
1376
GED
1378



WP_001040080
1368
GED
1370



WP_001040081
1368
GED
1370



WP_001040083
1368
GED
1370



WP_001040085
1368
GED
1370



WP_001040087
1368
GED
1370



WP_001040088
1368
GGD
1370



WP_001040089
1368
GED
1370



WP_001040090
1368
GED
1370



WP_001040091
1368
GED
1370



WP_001040092
1368
GED
1370



WP_001040094
1368
GED
1370



WP_001040095
1368
GEG
1370



WP_001040096
1368
GEG
1370



WP_001040097
1368
GED
1370



WP_001040098
1368
GED
1370



WP_001040099
1368
GED
1370



WP_001040100
1368
GED
1370



WP_001040104
1368
GED
1370



WP_001040105
1368
GED
1370



WP_001040106
1368
GED
1370



WP_001040107
1368
GED
1370



WP_001040108
1368
GED
1370



WP_001040109
1368
GED
1370



WP_001040110
1368
GED
1370



WP_015058523
1368
GED
1370



WP_017643650
1368
GED
1370



WP_017647151
1368
GED
1370



WP_017648376
1368
GED
1370



WP_017649527
1368
GED
1370



WP_017771611
1368
GED
1370



WP_017771984
1368
GED
1370



CFQ25032
1368
GED
1370



CFV16040
1368
GED
1370



KLJ37842
1368
GED
1370



KLJ72361
1368
GGD
1370



KLL20707
1382
GED
1384



KLL42645
1368
GED
1370



WP_047207273
1368
GED
1370



WP_047209694
1368
GED
1370



WP_050198062
1368
GED
1370



WP_050201642
1368
GED
1370



WP_050204027
1368
GED
1370



WP_050881965
1368
GED
1370



WP_050886065
1368
GED
1370



AHN30376
1368
GED
1370



EA078426
1368
GED
1370



CCW42055
1368
GED
1370



WP_003041502
1384
GED
1386



WP_037593752
1344
GED
1346



WP_049516684
1344
GED
1346



GAD46167
1343
GED
1345



WP_018363470
1375
GEE
1377



WP_003043819
1373
GGD
1375



WP_006269658
1343
GED
1345



WP_048800889
1363
GED
1365



WP_012767106
1369
GGD
1371



WP_014612333
1369
GGD
1371



WP_015017095
1369
GGD
1371



WP_015057649
1369
GGD
1371



WP_048327215
1369
GGD
1371



WP_049519324
1369
GGD
1371



WP_012515931
1346
GEN
1348



WP_021320964
1346
GEN
1348



WP_037581760
1346
GEN
1348



WP_004232481
1375
GEE
1377



WP_009854540
1368
GEE
1370



WP_012962174
1369
GEE
1371



WP_039695303
1370
GEE
1372



WP_014334983
1373
GEE
1375



WP_003099269
1366
GGK
1368



AHY15608

---




AHY17476

---




ESR09100
198
GGK
200



AGM98575

---




ALF27331
1343
GGD
1345



WP_018372492
1351
GEN
1353



WP_045618028
1374
GED
1376



WP_045635197
1368
GED
1370



WP_002263549
1343
GGD
1345



WP_002263887
1343
GGD
1345



WP_002264920
1343
GGD
1345



WP_002269043
1343
GGD
1345



WP_002269448
1343
GGD
1345



WP_002271977
1343
GGD
1345



WP_002272766
1343
GGD
1345



WP_002273241
1343
GGD
1345



WP_002275430
1343
GGD
1345



WP_002276448
1343
GGD
1345



WP_002277050
1353
GGD
1355



WP_002277364
1343
GGD
1345



WP_002279025
1343
GGD
1345



WP_002279859
1343
GGD
1345



WP_002280230
1343
GGD
1345



WP_002281696
1343
GGD
1345



WP_002282247
1353
GGD
1355



WP_002282906
1343
GGD
1345



WP_002283846
1343
GGD
1345



WP_002287255
1343
GGD
1345



WP_002288990
1343
GGD
1345



WP_002289641
1343
GGD
1345



WP_002290427
1343
GGD
1345



WP_002295753
1343
GGD
1345



WP_002296423
1343
GGD
1345



WP_002304487
1357
GGD
1359



WP_002305844
1343
GGD
1345



WP_002307203
1343
GGD
1345



WP_002310390
1343
GGD
1345



WP_002352408
1343
GGD
1345



WP_012997688
1343
GGD
1345



WP_014677909
1343
GGD
1345



WP_019312892
1343
GGD
1345



WP_019313659
1343
GGD
1345



WP_019314093
1343
GGD
1345



WP_019315370
1343
GGD
1345



WP_019803776
1343
GGD
1345



WP_019805234
1343
GGD
1345



WP_024783594
1343
GGD
1345



WP_024784288
1353
GGD
1355



WP_024784666
1343
GGD
1345



WP_024784894
1343
GGD
1345



WP_024786433
1353
GGD
1355



WP_049473442
1343
GGD
1345



WP_049474547
1343
GGD
1345



EMC03581
1336
GGD
1338



WP_000428612
1371
GED
1373



WP_000428613
1369
GED
1371



WP_049523028
1364
GEE
1366



WP_003107102
1335
GGD
1337



WP_054279288
1366
GGD
1368



WP_049531101
1374
GED
1376



WP_049538452
1374
GED
1376



WP_049549711
1376
GED
1378



WP_007896501
1372
GGD
1374



EFR44625
1324
GGD
1326



WP_002897477
1368
GEE
1370



WP_002906454
1375
GED
1377



WP_009729476
1369
GED
1371



CQR24647
1359
GGE
1361



WP_000066813
1373
GED
1375



WP_009754323
1369
GED
1371



WP_044674937
1362
GGD
1364



WP_044676715
1364
GGD
1366



WP_044680361
1364
GGD
1366



WP_044681799
1362
GGD
1364



WP_049533112
1384
GED
1386



WP_029090905

---




WP_006506696

---




A1T42264
1366
GGD
1389



WP_034440723






AKQ21048
1366
GGD
1384



WP_004636532
1330
-ED
1332



WP_002364836
1336
-VD
1337



WP_016631044
1287
-VD
1288



EMS75795
1077
GEQ
1079



WP_002373311
1336
-VD
1337



WP_002378009
1336
-VD
1337



WP_002407324
1336
-VD
1337



WP_002413717
1336
-VD
1337



WP_010775580
1338
-VD
1339



WP_010818269
1336
-VD
1337



WP_010824395
1336
-VD
1337



WP_016622645
1336
-VD
1337



WP_033624816
1336
-VD
1337



WP_033625576
1336
-VD
1337



WP_033789179
1336
-VD
1337



WP_002310644

---




WP_002312694

---




WP_002314015

---




WP_002320716

---




WP_002330729

---




WP_002335161

---




WP_002345439

---




WP_034867970
1334
GEQ
1336



WP_047937432

---




WP_010720994
1334
GEQ
1336



WP_010737004
1334
GEQ
1336



WP_034700478
1334
GEQ
1336



WP_007209003

---




WP_023519017
1327
GER
1330



WP_010770040
1333
-VD
1334



WP_048604708
1329
-GD
1330



WP_010750235
1337
GVQ
1339



AII16583
1405
GGD
1424



WP_029073316

---




WP_031589969

---




KDA45870

---




WP_039099354

---




AKP02966

---




WP_010991369
1333
-DD
1334



WP_033838504
1333
-DD
1334



EHN60060
1336
-DD
1337



EFR89594
1102
-DD
1103



WP_038409211
1333
-ED
1334



EFR95520
952
-ED
953



WP_003723650
1333
-DD
1334



WP_003727705
1333
-DD
1334



WP_003730785
1333
-DD
1334



WP_003733029
1333
-DN
1334



WP_003739838
1333
-DG
1334



WP_014601172
1333
-DD
1334



WP_023548323
1333
-DS
1334



WP_031665337
1333
-DD
1334



WP_031669209
1333
-DN
1334



WP_033920898
1333
-DS
1334



AKI42028
1336
-DD
1337



AKI50529
1336
-DS
1337



EFR83390
781
-DD
782



WP_046323366
1333
-DD
1334



AKE81011
1382
GGD
1400



CUO82355

---




WP_033162887

---




AGZ01981
1399
GGD
1417



AKA60242
1366
GGD
1368



AKS40380
1366
GGD
1376



4UN5_B
1370
GGD
1372
















TABLE 2







T to C changes with NGG PAM. Table 2 shows a list of T to C mutations that may


be corrected using any of the base editors provided herein. GRNAs and gRNAall indicate the


protospacer and PAM sequence, where the PAM sequence is the last 3 nucleotides of each of


the sequences in GRNAs and gRNAall.


















SEQ

SEQ

SEQ




Gene
Gene
ID

ID

ID



Name
ID
Symbol
NO:
Flanks
NO:
GRNAs
NO:
gRNAall


















NM_000071.2
875
CBS
2540
[′CTGAAGCCGC
2703-
[′ATCAYTGGGGTG
2907-
[′ATCAYTGGGGTG


(CBS):c.833T>C



GCCCTCTGCAG
2704
GATCCCGAAGG′,
2908
GATCCCGAAGG′,


(p.Ile278Thr)



ATCAYTGGGGT

′TCAYTGGGGTGGA

′TCAYTGGGGTGG






GGATCCCGAA

TCCCGAAGGG′]

ATCCCGAAGGG′]






GGGTCCATC′]






NM_001385.2
1807
DPYS
2541
[′TGTTGAAGAT
2705-
[′CGTAATAYGGGA
2909-
[′CGTAATAYGGGA


(DPYS):c.1078T>C



CGGATGTCCGT
2707
AAAAGGCGTGG′,
2911
AAAAGGCGTGG′,


(p.Trp360Arg)



AATAYGGGAA

′AATAYGGGAAAA

′AATAYGGGAAAA






AAAGGCGTGG

AGGCGTGGTGG′,

AGGCGTGGTGG′,






TGGGTTTCAC′]

′ATAYGGGAAAAA

′ATAYGGGAAAAA








GGCGTGGTGGG′]

GGCGTGGTGGG′]


NM_000027.3
175
AGA
2542
[′TCCAGAATTC
2708
[′GTTATAYGTGCC
2912
[′GTTATAYGTGCC


(AGA):c.916T>C



TTTGGGGCTGT

AATGTGACTGG′]

AATGTGACTGG′]


(p.Cys306Arg)



TATAYGTGCCA










ATGTGACTGGA










AGTTACGG′]






NM_000035.3
229
ALDOB
2543
[′GAAAGATGGT
2709
[′GGAAGYGGCGTG
2913
[′GGAAGYGGCGT


(ALDOB):c.442T>C



GTTGACTTTGG

CTGTGCTGAGG′]

GCTGTGCTGAGG′]


(p.Trp148Arg)



GAAGYGGCGT










GCTGTGCTGAG










GATTGCCGA′]






NM_173560.3
222546
RFX6
2544
[′GCAGACACAG
2710-
[′CAGTGGYGAGAC
2914-
[′CAGTGGYGAGAC


(RFX6):c.380+2T>C



CTCACGCTGCA
2711
TCGCCCGCAGG′,
2915
TCGCCCGCAGG′,






GTGGYGAGAC

′AGTGGYGAGACTC

′AGTGGYGAGACT






TCGCCCGCAGG

GCCCGCAGGG′]

CGCCCGCAGGG′]






GTACACTGA′]






NM_153704.5
91147
TMEM67
2545
[′AGAACGTTTT
2712
[′TGGAHGTGCCTTT
2916
[′TGGAHGTGCCTT


(TMEM67):c.1843T>C



GTCACTTATGT

GCTCTGAAGG′]

TGCTCTGAAGG′]


(p.Cys615Arg)



TGGAHGTGCCT










TTGCTCTGAAG










GTAAGTTT′]






NM_000124.3
2074
ERCC6
2546
[′AAGCAGTTTT
2713
[′TGCYAAAAGACC
2917
[′TGCYAAAAGACC


(ERCC6):c.2960T>C



TGACAAATAG

CAAAACAAAGG′]

CAAAACAAAGG′]


(p.Leu987Pro)



AGTGCYAAAA










GACCCAAAAC










AAAGGCGGTTT′]






NM_020435.3
57165
GJC2
2547
[′TGCCTGCTGC
2714
[′TGAGAYGGCCCA
2918-
[′TGAGAYGGCCCA


(GJC2):c.857T>C



TCAACCTCTGT

CCTGGGCTTGG′]
2919
CCTGGGCTTGG′,


(p.Met286Thr)



GAGAYGGCCC



′GAGAYGGCCCAC






ACCTGGGCTTG



CTGGGCTTGGG′]






GGCAGCGCG′]






NM_000920.3
5091
PC
2548
[′CGGTTTATTG
2715
[′CCAGAAGBGGTC
2920
[′CCAGAAGBGGTC


(PC):c.434T>C



GGCCAAGCCC

CGCAAGATGGG′]

CGCAAGATGGG′]


(p.Val145Ala)



AGAAGBGGTC










CGCAAGATGG










GAGACAAGGTG′]






NM_000026.2
158
ADSL
2549
[′TCCAAGGTAG
2716
[′AAGAYGGTGACA
2921
[′AAGAYGGTGAC


(ADSL):c.674T>C



AGCAGCTTGAC

GAAAAGGCAGG′]

AGAAAAGGCAGG′]


(p.Met225Thr)



AAGAYGGTGA










CAGAAAAGGC










AGGATTTAAG′]






NM_000391.3
1200
TPP1
2550
[′TCTCTCAGGT
2717
[′GCCGGGYGTTGG
2922
[′GCCGGGYGTTGG


(TPP1):c.1093T>C



GACAGTGGGG

TCTGTCTCTGG′]

TCTGTCTCTGG′]


(p.Cys365Arg)



CCGGGYGTTG










GTCTGTCTCTG










GAAGACACCA′]






NM_004183.3
7439
BEST1
2551
[′TACGACTGGA
2718
[′CACTGGYGTATA
2923
[′CACTGGYGTATA


(BEST1):c.704T>C



TTAGTATCCCA

CACAGGTGAGG′]

CACAGGTGAGG′]


(p.Val235Ala)



CTGGYGTATAC










ACAGGTGAGG










ACTAGGCTG′]






NM_000019.3
38
ACAT1
2552
[′CTCAATGTTA
2719
[′CAAGAAYAGTAG
2924
[′CAAGAAYAGTA


(ACAT1):c.935T>C



CACCACTGGCA

GTAAGGCCAGG′]

GGTAAGGCCAGG′]


(p.Ile312Thr)



AGAAYAGTAG










GTAAGGCCAG










GCGAGGTGGC′]






NM_000543.4
6609
SMPD1
2553
[′CGGGCCCTGA
2720
[′CACYTGTGAGGA
2925-
[′AGCACYTGTGAG


(SMPD1):c.911T>C



CCACCGTCACA

AGTTCCTGGGG′]
2927
GAAGTTCCTGG′,


(p.Leu304Pro)



GCACYTGTGA



′GCACYTGTGAGG






GGAAGTTCCTG



AAGTTCCTGGG′,






GGGCCAGTG′]



′CACYTGTGAGGA










AGTTCCTGGGG′]


NM_000527.4
3949
LDLR
2554
[′ACAAATCTGA
2721
[′CGGYATGGGCGG
2928-
[′ACTGCGGYATGG


(LDLR):c.694+2T>C



CGAGGAAAAC

GGCCAGGGTGG′]
2930
GCGGGGCCAGG′,






TGCGGYATGG



′CTGCGGYATGGG






GCGGGGCCAG



CGGGGCCAGGG′,






GGTGGGGGCGG′]



′CGGYATGGGCGG










GGCCAGGGTGG′]


NM_012464.4
7092
TLL1
2555
[′AAGAACTGTG
2722
[′GGGATTGYTGTTC
2931
[′GGGATTGYTGTT


(TLL1):c.713T>C



ATAAATTTGGG

ATGAATTGGG′]

CATGAATTGGG′]


(p.Val238Ala)



ATTGYTGTTCA










TGAATTGGGTC










ATGTGATA′]






NM_000112.3
1836
SLC26A2
2556
[′CCTGCAGCGG
2723
[′GAGAGGYGAGAA
2932
[′GAGAGGYGAGA


(SLC26A2):c.-26+2T>C



CCCGGACCCG

GAGGGAAGCGG′]

AGAGGGAAGCGG′]






AGAGGYGAGA










AGAGGGAAGC










GGACCAGGGA










A′]






NM_001005741.2
2629
GBA
2557
[′CATCTACCAC
2724
[′GCCAGAYACTTT
2933-
[′GCCAGAYACTTT


(GBA):c.751T>C



CAGACCTGGG

GTGAAGTAAGG′]
2934
GTGAAGTAAGG′,


(p.Tyr251His)



CCAGAYACTTT



′CCAGAYACTTTGT






GTGAAGTAAG



GAAGTAAGGG′]






GGATCAGCAA′]






NM_020365.4
8891
EIF2B3
2558
[′CCACCAGTCC
2725
[′CCAGAYTGTCAG
2935
[′CCAGAYTGTCAG


(EIF2B3):c.1037T>C



ATTCGTCAGCC

CAAACACCTGG′]

CAAACACCTGG′]


(p.Ile346Thr)



CAGAYTGTCA










GCAAACACCT










GGTAAGTGCT′]






NM_022041.3
8139
GAN
2559
[′TGCTATGCAG
2726
[′AAGAAAAYCTAC
2936-2937
[′AAGAAAAYCTAC


(GAN):c.1268T>C



CTATGAAAAA

GCCATGGGTGG′]

GCCATGGGTGG′,


(p.Ile423Thr)



GAAAAYCTAC



′AAAAYCTACGCC






GCCATGGGTG



ATGGGTGGAGG′]






GAGGCTCCTAC′]






NM_054027.4
56172
ANKH
2560
[′GCTGTCAAGG
2727-
[′GTCGAGAYGCTG
2938-2939
[′GTCGAGAYGCTG


(ANKH):c.143T>C



AGGATGCAGT
2728
GCCAGCTACGG′,

GCCAGCTACGG′,


(p.Met48Thr)



CGAGAYGCTG

′TCGAGAYGCTGGC

′TCGAGAYGCTGG






GCCAGCTACG

CAGCTACGGG′]

CCAGCTACGGG′]






GGCTGGCGTAC′]






NM_006329.3
10516
FBLN5
2561
[′TTGCTTGCAT
2729
[′GACAYTGATGAA
2940
[′GACAYTGATGAA


(FBLN5):c.506T>C



TTCTGTTTCCA

TGTCGCTATGG′]

TGTCGCTATGG′]


(p.Ile169Thr)



GACAYTGATG










AATGTCGCTAT










GGTTACTGC′]






NM_004086.2
−1

2562
[′GCACCTCTGG
2730
[′AGATAYGGCTTC
2941
[′AGATAYGGCTTC


(COCH):c.1535T>C



ATGACCTGAA

TAAACCGAAGG′]

TAAACCGAAGG′]


(p.Met512Thr)



AGATAYGGCTT










CTAAACCGAA










GGAGTCTCAT′]






NM_002942.4
6092
ROBO2
2563
[′AATAGCAACA
2731
[′GAGAYTGGAAAT
2942
[′GAGAYTGGAAAT


(ROBO2):c.2834T>C



GTGGCCCAAAT

TTTGGCCGTGG′]

TTTGGCCGTGG′]


(p.Ile945Thr)



GAGAYTGGAA










ATTTTGGCCGT










GGAGGTAAG′]






NM_001300.5
1316
KLF6
2564
[′CAAATTTGAC
2732
[′TCTGYGGACCAA
2943
[′TCTGYGGACCAA


(KLF6):c.190T>C



AGCCAGGAAG

AATCATTCTGG′]

AATCATTCTGG′]


(p.Trp64Arg)



ATCTGYGGACC










AAAATCATTCT










GGCTCGGGA′]






NM_030653.3
1663
DDX11
2565
[′CTGGCATATT
2733
[′TCCAGGYGCGGG
2944-2945
[′TCCAGGYGCGGG


(DDX11):c.2271+2T>C



CCAGGTGCATC

CGTCATGCTGG′]

CGTCATGCTGG′,






CAGGYGCGGG



′CCAGGYGCGGGC






CGTCATGCTGG



GTCATGCTGGG′]






GCTTGGGTC′]






NM_001451.2
2294
FOXF1
2566
[′CCAAGACATC
2734
[′TGATGYGAGGCT
2946
[′TGATGYGAGGCT


(FOXF1):c.1138T>C



AAGCCTTGCGT

GCCGCCGCAGG′]

GCCGCCGCAGG′]


(p.Ter380Arg)



GATGYGAGGC










TGCCGCCGCAG










GCCCTCCTG′]






NM_000435.2
4854
NOTCH3
2567
[′CCTCGACCGC
2735
[′ACCYGTATCTGTA
294-72948
[′TTCACCYGTATC


(NOTCH3):c.1363T>C



ATAGGCCAGTT

TGGCAGGTGG′]

TGTATGGCAGG′,


(p.Cys455Arg)



CACCYGTATCT



′ACCYGTATCTGTA






GTATGGCAGGT



TGGCAGGTGG′]






GGGTGGTG′]






NM_002427.3
4322
MMP13
2568
[′CTTGACGATA
2736-
[′GTCAYGAAAAAG
2949-2950
[′GTCAYGAAAAA


(MMP13):c.272T>C



ACACCTTAGAT
2737
CCAAGATGCGG′,

GCCAAGATGCGG′,


(p.Met91Thr)



GTCAYGAAAA

′TCAYGAAAAAGCC

′TCAYGAAAAAGC






AGCCAAGATG

AAGATGCGGG′]

CAAGATGCGGG′]






CGGGGTTCCT′]






NM_000211.4
3689
ITGB2
2569
[′GATGACCTCA
2738
[′AGCYAGGTGGCG
2951
[′AGCYAGGTGGCG


(ITGB2):c.446T>C



GGAATGTCAA

ACCTGCTCCGG′]

ACCTGCTCCGG′]


(p.Leu149Pro)



GAAGCYAGGT










GGCGACCTGCT










CCGGGCCCTC′]






NM_005502.3
19
ABCA1
2570
[′CAAAATCAAG
2739-
[′CCTGTGYGTCCCC
2952-2955
[′CCTGTGYGTCCC


(ABCA1):c.4429T>C



AAGATGCTGCC
2740
CAGGGGCAGG′,

CCAGGGGCAGG′,


(p.Cys1477Arg)



TGTGYGTCCCC

′CTGTGYGTCCCCC

′CTGTGYGTCCCCC






CAGGGGCAGG

AGGGGCAGGG′]

AGGGGCAGGG′,






GGGGCTGCC′]



′TGTGYGTCCCCCA










GGGGCAGGGG′,










′GTGYGTCCCCCA










GGGGCAGGGGG′]


m.12297T>C
4568
MT-TL2
2571
[′AAAGGATAAC
2741
[′GTCYTAGGCCCC
2956
[′GTCYTAGGCCCC






AGCTATCCATT

AAAAATTTTGG′]

AAAAATTTTGG′]






GGTCYTAGGCC










CCAAAAATTTT










GGTGCAAC′]






m.4290T>C
4565
MT-TI
2572
[′AAATATGTCT
2742
[′ACTYTGATAGAG
2957
[′ACTYTGATAGAG






GATAAAAGAG

TAAATAATAGG′]

TAAATAATAGG′]






TTACTYTGATA










GAGTAAATAA










TAGGAGCTTA′]






m.4291T>C
4565
MT-TI
2573
[′AATATGTCTG
2743
[′ACTTYGATAGAG
2958
[′ACTTYGATAGAG






ATAAAAGAGT

TAAATAATAGG′]

TAAATAATAGG′]






TACTTYGATAG










AGTAAATAAT










AGGAGCTTAA′]






m.3394T>C
4535
MT-ND1
2574
[′GCTTACCGAA
2744
[′GGCYATATACAA
2959
[′GGCYATATACAA






CGAAAAATTCT

CTACGCAAAGG′]

CTACGCAAAGG′]






AGGCYATATA










CAACTACGCA










AAGGCCCCAA′]






NM_002764.3
5631
PRPS1
2575
[′ATCTCAGCCA
2745
[′GCAAATAYGCTA
2960
[′GCAAATAYGCTA


(PRPS1):c.344T>C



AGCTTGTTGCA

TCTGTAGCAGG′]

TCTGTAGCAGG′]


(p.Met115Thr)



AATAYGCTATC










TGTAGCAGGTG










CAGATCAT′]






NM_000132.3
2157
F8
2576
[′AGAGCAGAA
2746
[′TCAYGGTGAGTT
2961
[′TCAYGGTGAGTT


(F8):c.5372T>C



GTTGAAGATA

AAGGACAGTGG′]

AAGGACAGTGG′]


(p.Met1791Thr)



ATATCAYGGTG










AGTTAAGGAC










AGTGGAATTAC′]






NM_000132.3
2157
F8
2577
[′CCTTTCAATA
2747
[′AACAGAYAATGT
2962
[′AACAGAYAATGT


(F8):c.1754T>C



TATGTAATTAA

CAGACAAGAGG′]

CAGACAAGAGG′]


(p.Ile585Thr)



CAGAYAATGT










CAGACAAGAG










GAATGTCATC′]






NM_000133.3
2158
F9
2578
[′TGTGCAATGA
2748
[′GAAYATATACCA
2963
[′GAAYATATACCA


(F9):c.1328T>C



AAGGCAAATA

AGGTATCCCGG′]

AGGTATCCCGG′]


(p.Ile443Thr)



TGGAAYATAT










ACCAAGGTATC










CCGGTATGTC′]






NM_000169.2
−1

2579
[′TTATTTCATTC
2749
[′CAGTTAGYGATT
2964
[′CAGTTAGYGATT


(GLA):c.806T>C



TTTTTCTCAGT

GGCAACTTTGG′]

GGCAACTTTGG′]


(p.Val269Ala)



TAGYGATTGGC










AACTTTGGCCT










CAGCTGG′]






NM_000116.4
6901
TAZ
2580
[′CTCCCACTTC
2750
[′AAGYGTGTGCCT
2965
[′AAGYGTGTGCCT


(TAZ):c.352T>C



TTCAGCTTGGG

GTGTGCCGAGG′]

GTGTGCCGAGG′]


(p.Cys118Arg)



CAAGYGTGTG










CCTGTGTGCCG










AGGTGAGCT′]






NM_000061.2
695
BTK
2581
[′GGTGAACTCC
2751
[′AGCTAYGGCCGC
2966
[′AGCTAYGGCCGC


(BTK):c.2T>C



AGAAAGAAGA

AGTGATTCTGG′]

AGTGATTCTGG′]


(p.Met1Thr)



AGCTAYGGCC










GCAGTGATTCT










GGAGAGCATC′]






NM_000061.2
695
BTK
2582
[′AAGGACCTGA
2752
[′AGCYGGGGACTG
2967-2968
[′GAGCYGGGGACT


(BTK):c.1223T>C



CCTTCTTGAAG

GACAATTTGGG′]

GGACAATTTGG′,


(p.Leu408Pro)



GAGCYGGGGA



′AGCYGGGGACTG






CTGGACAATTT



GACAATTTGGG′]






GGGGTAGTG′]






NM_000061.2
695
BTK
2583
[′CAAGTTCAGC
2753
[′ACATTYGGGCTTT
2969
[′ACATTYGGGCTT


(BTK):c.1741T>C



AGCAAATCTG

TGGTAAGTGG′]

TTGGTAAGTGG′]


(p.Trp581Arg)



ACATTYGGGCT










TTTGGTAAGTG










GATAAGATT′]






NM_014009.3
50943
FOXP3
2584
[′GATTCATCCC
2754
[′GACAGAGYTCCT
2970
[′GACAGAGYTCCT


(FOXP3):c.970T>C



CACCCTCTGAC

CCACAACATGG′]

CCACAACATGG′]


(p.Phe324Leu)



AGAGYTCCTCC










ACAACATGGA










CTACTTCAA′]






NM_003688.3
8573
CASK
2585
[′TGAGCTCGTG
2755-
[′CACAGYGGGTCC
2971-2972
[′CACAGYGGGTCC


(CASK):c.2740T>C



TGCACAGCCCC
2756
CTGTCTCCTGG′,

CTGTCTCCTGG′,


(p.Trp914Arg)



ACAGYGGGTC

′ACAGYGGGTCCCT

′ACAGYGGGTCCC






CCTGTCTCCTG

GTCTCCTGGG′]

TGTCTCCTGGG′]






GGTCTATTA′]






NM_004992.3
4204
MECP2
2586
[′GACACATCCC
2757
[′GATTBTGACTTCA
2973-2974
[′GATTBTGACTTC


(MECP2):c.464T>C



TGGACCCTAAT

CGGTAACTGG′]

ACGGTAACTGG′,


(p.Phe155Ser)



GATTBTGACTT



′ATTBTGACTTCAC






CACGGTAACTG



GGTAACTGGG′]






GGAGAGGG′]






NM_000431.3
4598
MVK
2587
[′ATCGTGGCCC
2758
[′CTCAAYAGATGC
2975
[′CTCAAYAGATGC


(MVK):c.803T>C



CCCTCCTGACC

CATCTCCCTGG′]

CATCTCCCTGG′]


(p.Ile268Thr)



TCAAYAGATG










CCATCTCCCTG










GAGTGTGAG′]






NM_021961.5
7003
TEAD1
2588
[′TGAACACGGA
2759
[′TCATATTYACAG
2976
[′TCATATTYACAG


(TEAD1):c.1261T>C



GCACAACATC

GCTTGTAAAGG′]

GCTTGTAAAGG′]


(p.Tyr?His)



ATATTYACAGG










CTTGTAAAGGA










CTGAACATG′]






NM_005633.3
6654
SOS1
2589
[′CGAGATTCAG
2760
[′GGTYGGGAGGGA
2977
[′GGTYGGGAGGG


(SOS1):c.1294T>C



AAGAATATTG

AAAGACATTGG′]

AAAAGACATTGG′]


(p.Trp432Arg)



ATGGTYGGGA










GGGAAAAGAC










ATTGGACAGTG′]






NM_006920.4
−1

2590
[′TGTGGAAGAA
2761
[′AACAAYGGTGGA
2978
[′AACAAYGGTGG


(SCN1A):c.3577T>C



GGCAGAGGAA

ACCTGAGAAGG′]

AACCTGAGAAGG′]


(p.Trp1193Arg)



AACAAYGGTG










GAACCTGAGA










AGGACGTGTTT′]






NM_000141.4
2263
FGFR2
2591
[′TGTAACTTTT
2762-
[′TGGGGAAYATAC
2979-2980
[′TGGGGAAYATAC


(FGFR2):c.1018T>C



GAGGACGCTG
2763
GTGCTTGGCGG′,

GTGCTTGGCGG′,


(p.Tyr340His)



GGGAAYATAC

′GGGGAAYATACGT

′GGGGAAYATACG






GTGCTTGGCGG

GCTTGGCGGG′]

TGCTTGGCGGG′]






GTAATTCTAT′]






NM_000174.4
2815
GP9
2592
[′GGCCACCAAG
2764
[′CCCAYGTACCTG
2981
[′CCCAYGTACCTG


(GP9):c.70T>C



GACTGCCCCAG

CCGCGCCCTGG′]

CCGCGCCCTGG′]


(p.Cys24Arg)



CCCAYGTACCT










GCCGCGCCCTG










GAAACCAT′]






NM_000175.3
2821
GPI
2593
[′CTGGGAAAGC
2765
[′AAAABAGAGCCT
2982
[′AAAABAGAGCCT


(GPI):c.1574T>C



AGCTGGCTAA

GAGCTTGATGG′]

GAGCTTGATGG′]


(p.Ile525Thr)



GAAAABAGAG










CCTGAGCTTGA










TGGCAGTGCT′]






NM_000315.2
5741
PTH
2594
[′AGTTATGATT
2766
[′AATTYGTTTTCTT
2983
[′AATTYGTTTTCTT


(PTH):c.52T>C



GTCATGTTGGC

ACAAAATCGG′]

ACAAAATCGG′]


(p.Cys18Arg)



AATTYGTTTTC










TTACAAAATCG










GATGGGAA′]






NM_000222.2
3815
KIT
2595
[′CCCATGTATG
2767
[′AAGGNTGTTGAG
2984
[′AAGGNTGTTGAG


(KIT):c.1676T>C



AAGTACAGTG

GAGATAAATGG′]

GAGATAAATGG′]


(p.Val559Ala)



GAAGGNTGTT










GAGGAGATAA










ATGGAAACAAT′]






NM_016835.4
4137
MAPT
2596
[′AGTCCAAGTG
2768-
[′GGATAAYATCAA
2985-2986
[′GGATAAYATCAA


(MAPT):c.1839T>C



TGGCTCAAAG
2769
ACACGTCCCGG′,

ACACGTCCCGG′,


(p.Asn613=)



GATAAYATCA

′GATAAYATCAAAC

′GATAAYATCAAA






AACACGTCCCG

ACGTCCCGGG′]

CACGTCCCGGG′]






GGAGGCGGCA′]






NM_170707.3
4000
LMNA
2597
[′GAGATCCACG
2770
[′TCTYGGAGGGCG
2987
[′TCTYGGAGGGCG


(LMNA):c.1139T>C



CCTACCGCAAG

AGGAGGAGAGG′]

AGGAGGAGAGG′]


(p.Leu380Ser)



CTCTYGGAGG










GCGAGGAGGA










GAGGTGGGCT′]






NM_000424.3
3852
KRT5
2598
[′GCCACCATGT
2771-
[′TCAAGTGYGTCCT
2988-2991
[′TCAAGTGYGTCC


(KRT5):c.20T>C



CTCGCCAGTCA
2773
TCCGGAGCGG′,

TTCCGGAGCGG′,


(p.Val7Ala)



AGTGYGTCCTT

′CAAGTGYGTCCTT

′CAAGTGYGTCCTT






CCGGAGCGGG

CCGGAGCGGG′,

CCGGAGCGGG′,






GGCAGTCGT′]

′AAGTGYGTCCTTC

′AAGTGYGTCCTTC








CGGAGCGGGG′]

CGGAGCGGGG′,










′AGTGYGTCCTTCC










GGAGCGGGGG′]


NM_000184.2
3048
HBG2
2599
[′GTTGTCTACC
2774
[′CAGAGGTYCTTT
2992
[′CAGAGGTYCTTT


(HBG2):c.125T>C



CATGGACCCA

GACAGCTTTGG′]

GACAGCTTTGG′]


(p.Phe42Ser)



GAGGTYCTTTG










ACAGCTTTGGC










AACCTGTCC′]






NM_000515.4
2688
GH1
2600
[′AGGAAACAC
2775
[′TGAGYGGATGCC
2993
[′TGAGYGGATGCC


(GH1):c.291+6T>C



AACAGAAATC

TTCTCCCCAGG′]

TTCTCCCCAGG′]






CGTGAGYGGA










TGCCTTCTCCC










CAGGCGGGGAT′]






NM_002087.3
2896
GRN
2601
[′TCCTTGGTAC
2776
[′CCAYGTGGACCC
2994
[′CCAYGTGGACCC


GRN):c.2T>C



TTTGCAGGCAG

TGGTGAGCTGG′]

TGGTGAGCTGG′]


(p.Met1Thr)



ACCAYGTGGA










CCCTGGTGAGC










TGGGTGGCC′]






NM_001083112.2
2820
GPD2
2602
[′AGGTATAAGA
2777
[′AAGTYTGATGCA
2995
[′AAGTYTGATGCA


(GPD2):c.1904T>C



AGAGATTTCAT

GACCAGAAAGG′]

GACCAGAAAGG′]


(p.Phe635Ser)



AAGTYTGATGC










AGACCAGAAA










GGCTTTATT′]






NM_00101807
2908
NR3C1
2603
[′CTCAACATGT
2778
[′AAGYGATTGCAG
2996
[′AAGYGATTGCAG


7.1(NR3C1):c.1712T>C



TAGGAGGGCG

CAGTGAAATGG′]

CAGTGAAATGG′]


(p.Val571Ala)



GCAAGYGATT










GCAGCAGTGA










AATGGGCAAAG′]






NM_006306.3
8243
SMC1A
2621
[′GTGTTTGAAG
2798
[′AGAYTGGTGTGC
3017
[′AGAYTGGTGTGC


(SMC1A):c.2351T>C



AGTTTTGTCGG

GCAACATCCGG′]

GCAACATCCGG′]


(p.11e784Thr)



GAGAYTGGTG










TGCGCAACATC










CGGGAGTTT′]






NM_002242.4
−1

2622
[′TGGTGTAATG
2799
[′GTTDGTGGAAAG
3018
[′GTTDGTGGAAAG


(KCN.113):c.722T>C



GAGTGATAGT

ATGAAGAATGG′]

ATGAAGAATGG′]


(p.Leu241Pro)



ACGTTDGTGGA










AAGATGAAGA










ATGGACATTC′]






NM_000199.3
6448
SGSH
2623
[′CCCCAGCGTT
2800
[′TCCGGGGRTGAC
3019
[′TCCGGGGRTGAC


(SGSH):c.892T>C



TTGGGTGCTCC

ACCAGTAAGGG′]

ACCAGTAAGGG′]


(p.Ser298Pro)



GGGGRTGACA










CCAGTAAGGG










TTCAGCAGTG′]






NM_020191.2
56945
MRPS22
2624
[′CCAATAATTT
2801
[′ATCYTAGGGTAA
3020
[′ATCYTAGGGTAA


(MRPS22):c.644T>C



TCAAGGAAGA

GGTGACTTAGG′]

GGTGACTTAGG′]


(p.Leu215Pro)



AAATCYTAGG










GTAAGGTGACT










TAGGTTTTAT′]






NM_017882.2
54982
CLN6
2625
[′CCCATTCTTC
2802
[′AGCYGGTATTCC
3021
[′AGCYGGTATTCC


(CLN6):c.200T>C



CATTTGCTCCG

CTCTCGAGTGG′]

CTCTCGAGTGG′]


(p.Leu67Pro)



CAGCYGGTATT










CCCTCTCGAGT










GGTTTCCA′]






NM_014874.3
9927
MFN2
2626
[′GTAGTCCTCA
2803
[′AATGWGAGTCAT
3022
[′AATGWGAGTCA


(MFN2):c.1392+2T>C



AGGTTTATAAG

GGAGCAACAGG′]

TGGAGCAACAGG′]






AATGWGAGTC










ATGGAGCAAC










AGGTCCTCTT′]






NM_024599.5
79651
RHBDF2
2627
[′GCTTACCGCC
2804
[′AGAYTGTGGATC
3023
[′AGAYTGTGGATC


(RHBDF2):c.557T>C



CCCCTCCCTTC

CGCTGGCCCGG′]

CGCTGGCCCGG′]


(p.11e186Thr)



CAGAYTGTGG










ATCCGCTGGCC










CGGGGCCGG′]






NM_020894.2
57654
UVSSA
2628
[′GAAAATGAA
2805
[′AAAATTYGCAAG
3024-3025
[′AAAATTYGCAAG


(UVSSA):c.94T>C



GGAACTGAAG

TATGTCTTAGG′]

TATGTCTTAGG′,


(p.Cys32Arg)



AAAATTYGCA



′AAATTYGCAAGT






AGTATGTCTTA



ATGTCTTAGGG′]






GGGTTCAGTAA′]






NM_001161581.1
25886
POC1A
2629
[′GCCAGTGATG
2806
[′AGCYGTGGGACA
3026
[′AGCYGTGGGACA


(POC1A):c.398T>C



ACAAGACTGTT

AGAGCAGCCGG′]

AGAGCAGCCGG′]


(p.Leu133Pro)



AAGCYGTGGG










ACAAGAGCAG










CCGGGAATGT′]






NM_005340.6
3094
HINT1
2630
[′ACACTTAATG
2807-
[′CAAGAAAYGTGC
3027-3028
[′CAAGAAAYGTGC


(HINT1):c.250T>C



ATTGTTGGCAA
2808
TGCTGATCTGG′,

TGCTGATCTGG′,


(p.Cys84Arg)



GAAAYGTGCT

′AAGAAAYGTGCTG

′AAGAAAYGTGCT






GCTGATCTGGG

CTGATCTGGG′]

GCTGATCTGGG′]






CCTGAATAA′]






NM_000495
1287
COL4A5
2631
[′TTTCCTGGTTT
2809
[′TCCAGYAAGTTA
3029-3030
[′CTCCAGYAAGTT


(COL4A5):c.438+2T>C



ACAGGGTCCTC

TAAAATTTGGG′]

ATAAAATTTGG′,






CAGYAAGTTAT



′TCCAGYAAGTTA






AAAATTTGGG



TAAAATTTGGG′]






ATTATGAT′]






NM_000344.3
6606
SMN1
2632
[′AACCTGTGTT
2810
[′CACTGGAYATGG
3031
[′CACTGGAYATGG


(SMN1):c.388T>C



GTGGTTTACAC

AAATAGAGAGG′]

AAATAGAGAGG′]


(p.Tyr130His)



TGGAYATGGA










AATAGAGAGG










AGCAAAATCT′]






NM_005334.2
3054
HCFC1
2633
[′TTAGTTGTTA
2811
[′CAAGAYGGCGGC
3032
[′CAAGAYGGCGG


(HCFC1):c.-970T>C



CTTCTTCACAC

TCCCAGGGAGG′]

CTCCCAGGGAGG′]






AAGAYGGCGG










CTCCCAGGGA










GGAGGCATGA′]






NM_000431.3
4598
MVK
2634
[′GTGGCATCAC
2812
[′CCAGGYATCCCG
3033-3034
[′CCAGGYATCCCG


(MVK):c.1039+2T>C



ACTCCTCAAGC

GGGGTAGGTGG′]

GGGGTAGGTGG′,






CAGGYATCCC



′CAGGYATCCCGG






GGGGGTAGGT



GGGTAGGTGGG′]






GGGCCAGGCT′]






NM_018344.5
55315
SLC29A3
2635
[′TATGAGGAAC
2813
[′ACTGATAYCAGG
3035-3036
[′ACTGATAYCAGG


(SLC29A3):c.607T>C



TCCCAGGCACT

TGAGAGCCAGG′]

TGAGAGCCAGG′,


(p.Ser203Pro)



GATAYCAGGT



′CTGATAYCAGGT






GAGAGCCAGG



GAGAGCCAGGG′]






GTCCGGGCAG′]






NM_000108.4
1738
DLD
2636
[′GTAGTTGATG
2815
[′ACAGTTAYAGGT
3037-3038
[′ACAGTTAYAGGT


(DLD):c.140T>C



CTGATGTAACA

TCTGGTCCTGG′,

TCTGGTCCTGG′,


(p.Ile47Thr)



GTTAYAGGTTC

′GTTAYAGGTTCTG

′GTTAYAGGTTCTG






TGGTCCTGGAG

GTCCTGGAGG′]

GTCCTGGAGG′]






GATATGTT′]






NM_004333.4
673
BRAF
2637
[′GGACAAAGA
2816-
[′ATCATYTGGAAC
3039-3040
[′ATCATYTGGAAC


(BRAF):c.1403T>C



ATTGGATCTGG
2817
AGTCTACAAGG′,

AGTCTACAAGG′,


(p.Phe468Ser)



ATCATYTGGAA

′TCATYTGGAACAG

′TCATYTGGAACA






CAGTCTACAAG

TCTACAAGGG′]

GTCTACAAGGG′]






GGAAAGTGG′]






NM_000540.2
6261
RYR1
2638
[′CAGGAGGAGT
2818
[′CGCAYGATCCAC
3041
[′CGCAYGATCCAC


(RYR1):c.1205T>C



CCCAGGCCGCC

AGCACCAATGG′]

AGCACCAATGG′]


(p.Met402Thr)



CGCAYGATCC










ACAGCACCAA










TGGCCTATAC′]






NM_000256.3
4607
MYBPC3
2639
[′GTAGCACGGA
2819
[′AAAGGYGGGCCT
3042
[′AAAGGYGGGCCT


(MYBPC3):c.1351+2T>C



GCTCTTTGTGA

GGGACCTGAGG′]

GGGACCTGAGG′]






AAGGYGGGCC










TGGGACCTGA










GGATGTGGGA′]






NM_000256.3
4607
MYBPC3
2640
[′CCTCCTATCA
2820
[′CACGYGAGTGGC
3043-3044
CCATCCTCAGG′,






GCCTTCCGCCG

CATCCTCAGGG′]

′CACGYGAGTGGC


(MYBPC3):c.821+2T>C



CACGYGAGTG



CATCCTCAGGG′]






GCCATCCTCAG










GGCCTGGGG′]






NM_000257.3
4625
MYH7
2641
[′AAGAGTGCAG
2821
[′GGAGAYGGCCTC
3045
[′GGAGAYGGCCTC


(MYH7):c.2546T>C



AAAGAGAGAA

CATGAAGGAGG′]

CATGAAGGAGG′]


(p.Met849Thr)



GGAGAYGGCC










TCCATGAAGG










AGGAGTTCACA′]






NM_206933.2
7399
USH2A
2642
[′CGACACAACA
2822
[′ATATAGAYGCCT
3046
[′ATATAGAYGCCT


(USH2A):c.1606T>C



AGCCAGCCAT

CTGCTCCCAGG′]

CTGCTCCCAGG′]


(p.Cys536Arg)



ATAGAYGCCTC










TGCTCCCAGGA










GAGCTTCAC′]






NM_000059.3
675
BRCA2
2643
[′TAGATAAATT
2823
[′CTTAGGYAAGTA
3047
[′CTTAGGYAAGTA


(BRCA2):c.316+2T>C



CAAATTAGACT

ATGCAATATGG′]

ATGCAATATGG′]






TAGGYAAGTA










ATGCAATATGG










TAGACTGGG′]






NM_007294.3
672
BRCA1
2644
[′CTCTTCTTCC
2824
[′GGCYAGAAATCT
3048-3049
[′GGGCYAGAAATC


(BRCA1):c.5291T>C



AGATCTTCAGG

GTTGCTATGGG′]

TGTTGCTATGG′,


(p.Leu1764Pro)



GGGCYAGAAA



′GGCYAGAAATCT






TCTGTTGCTAT



GTTGCTATGGG′]






GGGCCCTTC′]






NM_00113008
3735
KARS
2645
[′AGCTTCTGGG
2825
[′TTCYATGATCTTC
3050-3051
[′CTTCYATGATCT


9.1(KARS):c.517T>C



GGAAAGCTCA

GAGGAGAGGG′]

TCGAGGAGAGG′,


(p.Tyr173His)



TCTTCYATGAT



′TTCYATGATCTTC






CTTCGAGGAG



GAGGAGAGGG′]






AGGGGGTGAA′]






NM_00128300
−1

2646
[′CGGGCCCCTC
2826
[′CTGTGTGYGCCA
3052
[′CTGTGTGYGCCA


9.1(RTEL1):c.3730T>C



TCAGCAGGCTG

GGGCTGTGGGG′]

GGGCTGTGGGG′]


(p.Cys1244Arg)



TGTGYGCCAG










GGCTGTGGGG










CAGAGGACGT′]






NM_005554.3
3853
KRT6A
2647
[′GAGATCGCCA
2827
[′TGCBGGAGGGTG
3053
[′TGCBGGAGGGTG


(KRT6A):c.1406T>C



CCTACCGCAAG

AGGAGTGCAGG′]

AGGAGTGCAGG′]


(p.Leu469Pro)



CTGCBGGAGG










GTGAGGAGTG










CAGGTGGGTA′]






NM_000218.2
3784
KCNQ1
2648
[′CTGGTCCGCC
2828
[′AGCAAGBACGTG
3054-3056
[′CAGCAAGBACGT


(KCNQ1):c.550T>C



GGCTGCCGCA

GGCCTCTGGGG′]

GGGCCTCTGGG′,


(p.Tyr184His)



GCAAGBACGT



′AGCAAGBACGTG






GGGCCTCTGGG



GGCCTCTGGGG′,






GGCGGCTGCG′]



′GCAAGBACGTGG


NM_198056.2
6331
SCN5A
2649
[′GAGATGGACG
2829
[′CCAGAHGGAGGA
3057
[′CCAGAHGGAGG


(SCN5A):c.5624T>C



CCCTGAAGATC

GAAGTTCATGG′]

AGAAGTTCATGG′]


(p.Met1875Thr)



CAGAHGGAGG










AGAAGTTCATG










GCAGCCAAC′]






NM_006920.4
6323
SCN1A
2650
[′TGTTGTGTTC
2830-
[′ACTTYTATAGTAT
3058-3059
[′ACTTYTATAGTA


(SCN1A):c.269T>C



CTGTCTTACAG
2831
TGAATAAAGG′,

TTGAATAAAGG′,


(p.Phe90Ser)



ACTTYTATAGT

′CTTYTATAGTATT

′CTTYTATAGTATT






ATTGAATAAA

GAATAAAGGG′]

GAATAAAGGG′]






GGGAAGGCC′]






NM_006920.4
6323
SCN1A
2651
[′TGTGTTCCTG
2832-
[′ACTTTTAYAGTAT
3060-3061
[′ACTTTTAYAGTA


(SCN1A):c.272T>C



TCTTACAGACT
2833
TGAATAAAGG′,

TTGAATAAAGG′,


(p.Ile91Thr)



TTTAYAGTATT

′CTTTTAYAGTATT

′CTTTTAYAGTATT






GAATAAAGGG

GAATAAAGGG′]

GAATAAAGGG′]






AAGGCCATC′]






NM_006514.3
6336
SCN10A
2652
[′GGAGTCAGGG
2834-
[′GAGGARGAGGGC
3062-3064
[′GAGGARGAGGG


(SCN10A):c.1661T>C



TTGCTGGGTTG
2836
TTCTAGGGAGG′,

CTTCTAGGGAGG′,


(p.Leu554Pro)



AGGARGAGGG

′AGGARGAGGGCTT

′AGGARGAGGGCT






CTTCTAGGGAG

CTAGGGAGGG′,

TCTAGGGAGGG′,






GGGGCCTTG′]

′GGARGAGGGCTTC

′GGARGAGGGCTT








TAGGGAGGGG′]

CTAGGGAGGGG′]


NM_000251.2
4436
MSH2
2653
[′AACAGATGTT
2837-
[′CTGGYAAAAAAC
3065-3066



(MSH2):c.2005+2T>C



CCACATCATTA
2838
CTGGTTTTTGG′,

[′CTGGYAAAAAAC






CTGGYAAAAA

′TGGYAAAAAACCT

CTGGTTTTTGG′,






ACCTGGTTTTT

GGTTTTTGGG′]

′TGGYAAAAAACC






GGGCTTTGT′]



TGGTTTTTGGG′]


NM_000251.2
4436
MSH2
2654
[′CCTCATCCAG
2839
[′AAGGAAYGTGTT
3067
[′AAGGAAYGTGTT


(MSH2):c.595T>C



ATTGGACCAA

TTACCCGGAGG′]

TTACCCGGAGG′]


(p.Cys199Arg)



AGGAAYGTGT










TTTACCCGGAG










GAGAGACTGC′]






NM_001005741.2
2629
GBA
2655
[′TTCACCGCTC
2840
[′GCCRAGTGGGTG
3068-3070
[′GAGCCRAGTGGG


(GBA):c.667T>C



CATTGGTCTTG

ATGTCCAGGGG′]

TGATGTCCAGG′,


(p.Trp223Arg)



AGCCRAGTGG



′AGCCRAGTGGGT






GTGATGTCCAG



GATGTCCAGGG′,






GGGCTGGCA′]



′GCCRAGTGGGTG










ATGTCCAGGGG′]


NM_003494.3
8291
DYSF
2656
[′GAGGTCAGCT
2841
[′ATGGYAAGGAGC
3071
[′ATGGYAAGGAG


(DYSF):c.1284+2T>C



TTGCGGGGAA

AAGGGAGCAGG′]

CAAGGGAGCAGG′]






AATGGYAAGG










AGCAAGGGAG










CAGGAGGGTTC′]
2842
[′CACTGYGAGTAA
3072
[′CACTGYGAGTAA


NM_012463.3
2354
ATP6V50A2
2657
[′ACCCGCATCC

GCTGGAAGTGG′]

GCTGGAAGTGG′]


(ATP6V0A2):c.825+2T>C



AGGATCTCTAC










ACTGYGAGTA










AGCTGGAAGT










GGATTGCCTC′]






NM_016725.2
2348
FOLR1
2658
[′ACAAGGGCTG
2843
[′AGGYGAGGGCTG
3073-3074
[′CTTCAGGYGAGG


(FOLR1):c.493+2T>C



GAACTGGACTT

GGGTGGGCAGG′]

GCTGGGGTGGG′,






CAGGYGAGGG



′AGGYGAGGGCTG






CTGGGGTGGG



GGGTGGGCAGG′]






CAGGAATGGA′]






NM_003764.3
8676
STX11
2659
[′GACATTCAGG
2844
[′TGCYGGTGGCCG
3075
[′TGCYGGTGGCCG


(STX11):c.173T>C



ATGAAAACCA

ACGTGAAGCGG′]

ACGTGAAGCGG′]


(p.Leu58Pro)



GCTGCYGGTG










GCCGACGTGA










AGCGGCTGGGA′]






NM_014714.3
9742
IFT140
2660
[′GGACCCCAAG
2845
[′GCAGYGTGAGCT
3076-3077
[′CAAGCAGYGTGA


(1FT140):c.4078T>C



GAGTCCATCAA

GCTCCTGGAGG′]

GCTGCTCCTGG′,


(p.Cys1360Arg)



GCAGYGTGAG



′GCAGYGTGAGCT






CTGCTCCTGGA



GCTCCTGGAGG′]






GGAACCAGA′]






NM_000531.5
5009
OTC
2661
[′GAAAACAGA
2846
[′ATCATGGYAAGC
3078
[′ATCATGGYAAGC


(OTC):c.1005+2T>C



AAGTGGACAA

AAGAAACAAGG′]

AAGAAACAAGG′]






TCATGGYAAG










CAAGAAACAA










GGAATGGAGGAT′]






NM_000531.5
5009
OTC
2662
[′CTAAAAAACT
2847
[′AAGAAABTAAAT
3079
[′AAGAAABTAAAT


(OTC):c.158T>C



TTACCGGAGA

ATATGCTATGG′]

ATATGCTATGG′]


(p.Ile53Thr)



AGAAABTAAA










TATATGCTATG










GCTATCAGCA′]






NM_000531.5
5009
OTC
2663
[′GAGAAAAGA
2848
[′ACAAGATYGTCT
3080
[′ACAAGATYGTCT


(OTC):c.284T>C



AGTACTCGAAC

ACAGAAACAGG′]

ACAGAAACAGG′]


(p.Leu95Ser)



AAGATYGTCTA










CAGAAACAGG










TAAGTCCACT′]






NM_000531.5
5009
OTC
2664
[′CGTCCTTTAC
2849
[′AGAAGAYGCTGT
3081
[′AGAAGAYGCTGT


(OTC):c.2T>C



ACAATTAAAA

TTAATCTGAGG′]

TTAATCTGAGG′]


(p.Met1Thr)



GAAGAYGCTG










TTTAATCTGAG










GATCCTGTTA′]






NM_000531.5
5009
OTC
2665
[′CCATCCTATC
2850
[′GGCTGATYACCT
3082-3083
[′GGCTGATYACCT


(OTC):c.526T>C



CAGATCCTGGC

CACGCTCCAGG′]

CACGCTCCAGG′,


(p.Tyr176His)



TGATYACCTCA



′GATYACCTCACG






CGCTCCAGGTT



CTCCAGGTTGG′]






GGTTTATT′]






NM_000531.5
5009
OTC
2666
[′GAAGCAGCGC
2851
[′ATGTATYAATTAC
3084
[′ATGTATYAATTA


(OTC):c.779T>C



ATGGAGGCAA

AGACACTTGG′]

CAGACACTTGG′]


(p.Leu260Ser)



TGTATYAATTA










CAGACACTTGG










ATAAGCATG′]






NM_000322.4
5961
PRPH2
2667
[′CCACCAGACG
2852-
[′ACCTGYGGGTGC
3085-3086
[′ACCTGYGGGTGC


(PRPH2):c.736T>C



GAGGAGCTCA
2853
GTGGCTGCAGG′,

GTGGCTGCAGG′,


(p.Trp246Arg)



ACCTGYGGGT

′CCTGYGGGTGCGT

′CCTGYGGGTGCG






GCGTGGCTGCA

GGCTGCAGGG′]

TGGCTGCAGGG′]






GGGCTGCCCT′]






NM_000211.4
3689
ITGB2
2668
[′CCCCTCACCC
2854
[′CATGYGAGTGCA
3087
[′CATGYGAGTGCA


(ITGB2):c.1877+2T>C



TGTGGCAAGTA

GGCGGAGCAGG′]

GGCGGAGCAGG′]






CATGYGAGTG










CAGGCGGAGC










AGGCAGGGCG′]






NM_015474.3
25939
SAMHD1
2669
[′TTTGTGTTGA
2855
[′GGTGTRAAGAGT
3088
[′GGTGTRAAGAGT


(SAMHD1):c.1106T>C



TAAGCTCTACG

TGCGAGTGTGG′]

TGCGAGTGTGG′]


(p.Leu369Ser)



GTGTRAAGAGT










TGCGAGTGTGG










AACATGTC′]






NM_001101.3
60
ACTB
2670
[′AACCCCAAGG
2856
[′GAGAAGAYGACC
3089
[′GAGAAGAYGAC


(ACTB):c.356T>C



CCAACCGCGA

CAGGTGAGTGG′]

CCAGGTGAGTGG′]


(p.Met119Thr)



GAAGAYGACC










CAGGTGAGTG










GCCCGCTACCT′]






NM_015713.4
50484
RRM2B
2671
[′CTCGATGAGA
2857
[′CCATAGRAACAG
3090
[′CCATAGRAACAG


(RRM2B):c.368T>C



ATTTGAAAGCC

CGAGCCTCTGG′]

CGAGCCTCTGG′]


(p.Phe123Ser)



ATAGRAACAG










CGAGCCTCTGG










AACCTGCAC′]






NM_015599.2
5238
PGM3
2672
[′TTGGTTGATC
2858
[′AATGTYGGCACC
3091
[′AATGTYGGCACC


(PGM3):c.248T>C



CTTTGGGTGAA

ATCCTGGGAGG′]

ATCCTGGGAGG′]


(p.Leu83Ser)



ATGTYGGCACC










ATCCTGGGAG










GAACATGCC′]






NM_002136.2
3178
HNRNPA1
2673
[′GAATTACAAC
2859-
[′TTCAAATBTTGGA
3092-3094
[′TTCAAATBTTGG


(HNRNPA1):c.817T>C



AATCAGTCTTC
2861
CCCATGAAGG′,

ACCCATGAAGG′,


(p.Phe273Leu)



AAATBTTGGAC

′TCAAATBTTGGAC

′TCAAATBTTGGAC






CCATGAAGGG

CCATGAAGGG′,

CCATGAAGGG′,






AGGAAATTT′]

′AATBTTGGACCCA

′AATBTTGGACCC








TGAAGGGAGG′]

ATGAAGGGAGG′]


NM_002136.2
3178
HNRNPA1
2674
[′TTTTGGACCC
2862
[′AATYTTGGAGGC
3095
[′AATYTTGGAGGC


(HNRNPA1):c.841T>C



ATGAAGGGAG

AGAAGCTCTGG′]

AGAAGCTCTGG′]


(p.Phe281Leu)



GAAATYTTGG










AGGCAGAAGC










TCTGGCCCCTA′]






NM_022552.4
1788
DNMT3A
2675
[′CGCAAAATAC
2863
[′GCGRAGAGGTGG




(DNMT3A):c.2705T>C



TCCTTCAGCGG

CGGATGACTGG′]
3096
[′GCGRAGAGGTGG


(p.Phe902Ser)



AGCGRAGAGG



CGGATGACTGG′]






TGGCGGATGA










CTGGCACGCT′]






NM_000076.2
1028
CDKN1C
2676
[′GCGCAAGAG
2864-
[′CCAAGYGAGTAC
3097-3099
[′CCAAGYGAGTAC


(CDKN1C):c.*5+2T>C



GCTGCGGTGA
2866
AGCGCACCTGG′,

AGCGCACCTGG′,






GCCAAGYGAG

′CAAGYGAGTACA

′CAAGYGAGTACA






TACAGCGCACC

GCGCACCTGGG′,

GCGCACCTGGG′,






TGGGGGGGCGC′]

′AAGYGAGTACAG

′AAGYGAGTACAG








CGCACCTGGGG′]

CGCACCTGGGG′]


NC_012920.1:m.9478T>C
4514
MTCO3
2677
[′ATAATCCTAT
2867
[′TCAGAAGYTTTTT
3100
[′TCAGAAGYTTTT






TTATTACCTCA

TCTTCGCAGG′]

TTCTTCGCAGG′]






GAAGYTTTTTT










CTTCGCAGGAT










TTTTCTGA′]






NM_002049.3
2623
GATA1
2678
[′CGCAGGTTAA
2868-
[′TCCAYGGAGTTC
3101-3103
[′CTCCAYGGAGTT


(GATA1):c.2T>C



TCCCCAGAGGC
2869
CCTGGCCTGGG′,

CCCTGGCCTGG′,


(p.Met1Thr)



TCCAYGGAGTT

′CCAYGGAGTTCCC

′TCCAYGGAGTTC






CCCTGGCCTGG

TGGCCTGGGG′]

CCTGGCCTGGG′,






GGTCCCTG′]



′CCAYGGAGTTCC










CTGGCCTGGGG′]


NM_005740.2
10126
DNAL4
2679
[′GAGAAATTCT
2870
[′CGAGGYATTGCC
3104
[′CGAGGYATTGCC


(DNAL4):c.153+2T>C



CCAACAACAA

AGCAGTGCAGG′]

AGCAGTGCAGG′]






CGAGGYATTG










CCAGCAGTGC










AGGCGGCCCCT′]






NM_001287223.1
11280
SCN11A
2680
[′GGGCTCTACT
2871
[′TTCAYTGTGGTCA
3105-3106
[′CTTCAYTGTGGT


(SCN11A):c.1142T>C



CAGTCTTCTTC

TTTTCCTGGG′]

CATTTTCCTGG′,


(p.Ile381Thr)



TTCAYTGTGGT



′TTCAYTGTGGTCA






CATTTTCCTGG



TTTTCCTGGG′]






GCTCCTTC′]






NM_001302946.1
51095
TRNT1
2681
[′TAATGAATAG
2872
[′ACTTYATTTGACT
3107
[′ACTTYATTTGAC


(TRNT1):c.497T>C



GTTTTGATGGC

ACTTTAATGG′]

TACTTTAATGG′]


(p.Leu166Ser)



ACTTYATTTGA










CTACTTTAATG










GTTATGAA′]






NM_178151.2
1641
DCX
2682
[′AGGTCTCTGA
2873
[′CAAAATAYGGAA
3108
[′CAAAATAYGGA


(DCX):c.2T>C



GGTTCCACCAA

CTTGATTTTGG′]

ACTTGATTTTGG′]


(p.Met1Thr)



AATAYGGAAC










TTGATTTTGGA










CACTTTGAC′]






NM_000169.2
−1

2683
[′TGGACATCTT
2874
[′GAGAGAAYTGTT
3109
[′GAGAGAAYTGTT


(GLA):c.758T>C



TTAACCAGGA

GATGTTGCTGG′]

GATGTTGCTGG′]


(p.Ile253Thr)



GAGAAYTGTT










GATGTTGCTGG










ACCAGGGGGT′]






NM_170707.3
4000
LMNA
2684
[′ATTGACAATG
2875
[′TGAGTYTGAGAG
3110
[′TGAGTYTGAGAG


(LMNA):c.710T>C



GGAAGCAGCG

CCGGCTGGCGG′]

CCGGCTGGCGG′]


(p.Phe237Ser)



TGAGTYTGAG










AGCCGGCTGG










CGGATGCGCTG′]






NM_000256.3
4607
MYBPC3
2685
[′CAGAAAGCCG
2876-
[′ACCATGGBGAGC
3111-3113
[′ACCATGGBGAGC


(MYBPC3):c.3330+2T>C



ACAAGAAGAC
2878
CCAGGGTCTGG′,

CCAGGGTCTGG′,






CATGGBGAGC

′CCATGGBGAGCCC

′CCATGGBGAGCC






CCAGGGTCTGG

AGGGTCTGGG′,

CAGGGTCTGGG′,






GGTCCCCACG′]

′CATGGBGAGCCCA

′CATGGBGAGCCC








GGGTCTGGGG′]

AGGGTCTGGGG′]


NM_005957.4
4524
MTHFR
2686
[′AGCGGGGGCT
2879-
[′GAAGGYGTGGTA
3114-3116
[′GAAGGYGTGGTA


(MTHFR):c.1530+2T>C



ATGTCTTCCAG
2881
GGGAGGCACGG′,

GGGAGGCACGG′,






AAGGYGTGGT

′AAGGYGTGGTAG

′AAGGYGTGGTAG






AGGGAGGCAC

GGAGGCACGGG′,

GGAGGCACGGG′,






GGGGTGCCCC′]

′AGGYGTGGTAGG

′AGGYGTGGTAGG








GAGGCACGGGG′]

GAGGCACGGGG′]


NM_000264.3
5727
PTCH1
2687
[′AACCCCTGGA
2882-
[′ATCATTGYGAGT
3117-3119
[′ATCATTGYGAGT


(PTCH1):c.3168+2T>C



CGGCCGGGAT
2884
GTATTATAAGG′,

GTATTATAAGG′,






CATTGYGAGTG

′TCATTGYGAGTGT

′TCATTGYGAGTGT






TATTATAAGGG

ATTATAAGGG′,

ATTATAAGGG′,






GCTTTGTGG′]

′CATTGYGAGTGTA

′CATTGYGAGTGT








TTATAAGGGG′]

ATTATAAGGGG′]


NM_000030.2
189
AGXT
2688
[′CTTCCTGGTT
2885
[′CATTYGGGGGCA
3120
[′CATTYGGGGGCA


(AGXT):c.322T>C



GGGGCCAATG

GCGAGCCGTGG′]

GCGAGCCGTGG′]


(p.Trp108Arg)



GCATTYGGGG










GCAGCGAGCC










GTGGACATCGG′]






NM_000023.2
6442
SGCA
2689
[′ACTCGGCAGA
2886
[′CTGGAGAYTGGG
3121
[′CTGGAGAYTGGG


(SGCA):c.371T>C



GGCTGGTGCTG

GACCCAGAAGG′]

GACCCAGAAGG′]


(p.Ile124Thr)



GAGAYTGGGG










ACCCAGAAGG










TACCTCTAGC′]






NM_001103.3
88
ACTN2
2690
[′GAGAAGCACC
2887
[′CCTAAAAYGTTG
3122
[′CCTAAAAYGTTG


(ACTN2):c.683T>C



TGGATATTCCT

GATGCTGAAGG′]

GATGCTGAAGG′]


(p.Met228Thr)



AAAAYGTTGG










ATGCTGAAGGT










GAGATGAAA′]






NM_001165963.1
−1

2691
[′ATTCCATCCA
2888
[′TTCYGGTTTGTCT
3123
[′TTCYGGTTTGTC


(SCN1A):c.4055T>C



TCATGAATGTG

TATATTCTGG′]

TTATATTCTGG′]


(p.Leu1352Pro)



CTTCYGGTTTG










TCTTATATTCT










GGCTAATT′]






NM_001165963.1
6323
SCN1A
2692
[′CTAATAAATT
2889
[′TGTGGHGGCCAT
3124
[′TGTGGHGGCCAT


(SCN1A):c.1265T>C



TGATCCTGGCT

GGCCTACGAGG′]

GGCCTACGAGG′]


(p.Val422Ala)



GTGGHGGCCA










TGGCCTACGAG










GAACAGAAT′]






NM_000426.3
3908
LAMA2
2693
[′GCAGAATCAG
2890-
[′TTGAYAGGGAGC
3125-3126
[′TTGAYAGGGAGC


(LAMA2):c.8282T>C



AACCAGCTCTT
2891
AAGCAGTTCGG′,

AAGCAGTTCGG′,


(p.Ile2761Thr)



TTGAYAGGGA

′TGAYAGGGAGCA

′TGAYAGGGAGCA






GCAAGCAGTTC

AGCAGTTCGGG′]

AGCAGTTCGGG′]






GGGCTTTCA′]






NM_000257.3
−1

2694
[′TCCCGGAAGC
2892
[′AGCYGATTGAGA
3127
[′AGCYGATTGAGA


(MYH7):c.5117T>C



TGGCGGAGCA

CTAGTGAGCGG′]

CTAGTGAGCGG′]


(p.Leu1706Pro)



GGAGCYGATT










GAGACTAGTG










AGCGGGTGCAG′]






NM_001399.4
1896
EDA
2695
[′TCTGACTCCC
2893-
[′ACCAGGKGAGTC
3128-3130
[′CACCAGGKGAGT


(EDA):c.396+2T>C



AGGACGGGCA
2894
ACCTAGTAGGG′,

CACCTAGTAGG′,






CCAGGKGAGT

′CCAGGKGAGTCAC

′ACCAGGKGAGTC






CACCTAGTAGG

CTAGTAGGGG′]

ACCTAGTAGGG′,






GGCGGCGGCG′]



′CCAGGKGAGTCA










CCTAGTAGGGG′]


NM_001848.2
1291
COL6A1
2696
[′TCCAGGGGAC
2895-
[′ACAAGGYGAGCG
3131-3132
[′ACAAGGYGAGC


(COL6A1):c.957+2T>C



CCAAGGGCTA
2896
TGGGCTGCTGG′,

GTGGGCTGCTGG′,






CAAGGYGAGC

′CAAGGYGAGCGT

′CAAGGYGAGCGT






GTGGGCTGCTG

GGGCTGCTGGG′]

GGGCTGCTGGG′]






GGAGGGGGGA′]






NM_000238.3
3757
KCNH2
2697
[′CTGCGTCATG
2897-
[′CTGTGAGYGTGC
3133-3134
[′CTGTGAGYGTGC


(KCNH2):c.1945+6T>C



CTCATTGGCTG
2898
CCAGGGGCGGG′,

CCAGGGGCGGG′,






TGAGYGTGCCC

′TGAGYGTGCCCAG

′TGAGYGTGCCCA






AGGGGCGGGC

GGGCGGGCGG′]

GGGGCGGGCGG′]






GGCGGGGAG′]






NM_021007.2
6326
SCN2A
2698
[′CTAATAAATT
2899
[′TGTGGYGGCCAT
3135
[′TGTGGYGGCCAT


(SCN2A):c.1271T>C



TGATCTTGGCT

GGCCTATGAGG′]

GGCCTATGAGG′]


(p.Val424Ala)



GTGGYGGCCA










TGGCCTATGAG










GAACAGAAT′]






NM_021007.2
6326
SCN2A
2699
[′TATGCAGCTG
2900-
[′CGAAATGYAAGT
3136-3137
[′CGAAATGYAAGT


(SCN2A):c.4308+2T>C



TTGATTCACGA
2901
CTAGTTAGAGG′,

CTAGTTAGAGG′,






AATGYAAGTCT

′GAAATGYAAGTCT

′GAAATGYAAGTC






AGTTAGAGGG

AGTTAGAGGG′]

TAGTTAGAGGG′]






AAATTGTTT′]






NM_000083.2
1180
CLCN1
2700
[′CCCCGCGAAG
2902-
[′CTTTGTYTGACAA
3138-3139
[′CTTTGTYTGACA


(CLCN1):c.1283T>C



CCATCAGTACT
2903
CAATACATGG′,

ACAATACATGG′,


(p.Phe428Ser)



TTGTYTGACAA

′TTTGTYTGACAAC

′TTTGTYTGACAAC






CAATACATGG

AATACATGGG′]

AATACATGGG′]






GTGAAACAC′]






NM_004550.4
4720
NDUFS2
2701
[′CATTATGCTC
2904
[′GGAGTGAYGCTT
3140
[′GGAGTGAYGCTT


(NDUFS2):c.875T>C



TCCACAGTGGA

CGGGGCTCAGG′]

CGGGGCTCAGG′]


(p.Met292Thr)



GTGAYGCTTCG










GGGCTCAGGC










ATCCAGTGG′]






NM_000546.5
7157
TP53
2702
[′CACACGCAAA
2905-
[′CTCGGRTAAGAT
3141-3143
[′ACTCGGRTAAGA


(TP53):c.584T>C



TTTCCTTCCAC
2906
GCTGAGGAGGG′,

TGCTGAGGAGG′,


(p.Ile195Thr)



TCGGRTAAGAT

′TCGGRTAAGATGC

′CTCGGRTAAGAT






GCTGAGGAGG

TGAGGAGGGG′]

GCTGAGGAGGG′,






GGCCAGACC′]



′TCGGRTAAGATG










CTGAGGAGGGG′]
















TABLE 3







A to G with NGG PAM. Table 2 shows a list of A to G mutations that may be


corrected using any of the base editors provided herein. GRNAs and gRNAall indicate the


protospacer and PAM sequence, where the PAM sequence is the last 3 nucleotides of each of


the sequences in GRNAs and gRNAall.


















SEQ

SEQ

SEQ




Gene
Gene
ID

ID

ID



Name
ID
Symbol
NO:
Flanks
NO:
GRNAs
NO:
gRNAall


















NM_017547.3
55572
FOXRED1
5084
[′GTGGGCCCCCACC
5261
[′CCACCCGCTAGT
5464-
[′CCCACCCGCTAG


(FOXRED1):c.1289A>G



CGCTAGTTGTCAVC

TGTCAVCATGT′]
5466
TTGTCAVCATG′,


(p.Asn430Ser)



ATGTACTTTGCTACT



′CCACCCGCTAGTT






GGCTTCAGT′]



GTCAVCATGT′,










′CCCGCTAGTTGTC










AVCATGTACT′]


NM_000071.2
875
CBS
5085
[′GGTGACTCCCCCAT
5262
[′CCCCATCCCGCA
5467-
[′CCCCCATCCCGC


(CBS):c.1150A>G



CCCGCAGGACCRAG

GGACCRAGTTC′]
5470
AGGACCRAGTT′,


(p.Lys384Glu)



TTCCTGAGCGACAG



′CCCCATCCCGCA






GTGGATGCT′]



GGACCRAGTTC′,










′CCCATCCCGCAG










GACCRAGTTCC′,










′CCATCCCGCAGG










ACCRAGTTCCT′]


NM_000552.3
7450
VWF
5086
[′GAGTGTACCAAAA
5263
[′CCAAAACGTGCC
5471
[′CCAAAACGTGCC


(VWF):c.2384A>G



CGTGCCAGAACTRT

AGAACTRTGAC′]

AGAACTRTGAC′]


(p.Tyr795Cys)



GACCTGGAGTGCAT










GAGCATGGGC′]






NM_000552.3
7450
VWF
5087
[′ACCTGCGGCCTGT
5264
[′CCTGTGTGGGAA
5472
[′CCTGTGTGGGAA


(VWF):c.1583A>G



GTGGGAATTACART

TTACARTGGCA′]

TTACARTGGCA′]


(p.Asn528Ser)



GGCAACCAGGGCGA










CGACTTCCTT′]






NM_000308.2
5476
CTSA
5088
[′CTTTAGAAATACC
5265
[′CCAGATCCTATT
5473
[′CCAGATCCTATT


(CTSA):c.1238A>G



AGATCCTATTATRTA

ATRTAATGGAG′]

ATRTAATGGAG′]


(p.Tyr413Cys)



ATGGAGATGTAGAC










ATGGCCTGC′]






NM_000277.1
5053
PAH
5089
[′TTCTATTTTCCCCC
5266
[′CCCCCAATTACA
5474-
[′CCCCCAATTACA


(PAH):c.916A>G



AATTACAGGAARTT

GGAARTTGGCC′]
5476
GGAARTTGGCC′,


(p.Ile306Val)



GGCCTTGCCTCTCTG



′CCCCAATTACAG






GGTGCACC′]



GAARTTGGCCT′,










′CCCAATTACAGG










AARTTGGCCTT′]


NM_000512.4
2588
GALNS
5090
[′TTGGTCCCCGCGCA
5267
[′CCGCGCAGCCCC
5477
[′CCGCGCAGCCCC


(GALNS):c.1460A>G



GCCCCAGCTCARCG

AGCTCARCGTG′]

AGCTCARCGTG′]


(p.Asn487Ser)



TGTGCAACTGGGCG










GTCATGGTA′]






NM_013319.2
29914
UBIAD1
5091
[′GTGCACGGGGCCG
5268
[′CCGGTAATTTGG
5478
[′CCGGTAATTTGG


(UBIAD1):c.305A>G



GTAATTTGGTCARC

TCARCACTTAC′]

TCARCACTTAC′]


(p.Asn102Ser)



ACTTACTATGACTTT










TCCAAGGGC′]






NM_013319.2
29914
UBIAD1
5092
[′AGCACCGAGGCCA
5269
[′CCATTCTCCATT
5479
[′CCATTCTCCATT


(UBIAD1):c.695A>G



TTCTCCATTCCARCA

CCARCAACACC′]

CCARCAACACC′]


(p.Asn232Ser)



ACACCAGGGACATG










GAGTCCGAC′]






NM_000275.2
4948
OCA2
5093
[′TGCCACTGCCATCG
5270
[′CCATCGGGGACC
5480
[′CCATCGGGGACC


(OCA2):c.1465A>G



GGGACCCTCCARAT

CTCCARATGTC′]

CTCCARATGTC′]


(p.Asn489Asp)



GTCATTATTGTTTCC










AACCAAGA′]






NM_001127255.1
−1

5094
[′CTCACAAACCTGG
5271
[′CCTGGACTTGAG
5481
[′CCTGGACTTGAG


(NLRP7):c.2738A>G



ACTTGAGTATCARC

TATCARCCAGA′]

TATCARCCAGA′]


(p.Asn913Ser)



CAGATAGCTCGTGG










ATTGTGGATT′]






NM_152783.4
728294
D2HGDH
5095
[′TGCCCTTGTCCCTC
5272
[′CCTCCAGGAGAT
5482-
[′CCCTCCAGGAGA


(D2HGDH):c.1315A>G



CAGGAGATGGTRAC

GGTRACCTGCA′]
5483
TGGTRACCTGC′,


(p.Asn439Asp)



CTGCACCTCAATGT



′CCTCCAGGAGAT






GACGGCGGA′]



GGTRACCTGCA′]


NM_022132.4
64087
MCCC2
5096
[′TGTGGCCTGTGCCC
5273
[′CCCAAGTGCCTA
5484
[′CCCAAGTGCCTA


(MCCC2):c.1309A>G



AAGTGCCTAAGDTA

AGDTAACCCTC′]

AGDTAACCCTC′]


(p.Ile437Val)



ACCCTCATCATTGG










GGGCTCCTA′]






NM_000022.2
100
ADA
5097
[′TTCCCAACCCCTTT
5274
[′CCCCTTTCTTCCC
5485-
[′CCCCTTTCTTCCC


(ADA):c.219-2A>G



CTTCCCTTCCCRGGG

TTCCCRGGGG′]
5487
TTCCCRGGGG′,






GCTGCCGGGAGGCT



′CCCTTTCTTCCCT






ATCAAAAG′]



TCCCRGGGGC′,










′CCTTTCTTCCCTT










CCCRGGGGCT′]


NM_017780.3
55636
CHD7
5098
[′TTTAGTAATTGCCC
5275
[′CCCCATTGTCCA
5488
[′CCCCATTGTCCA


(CHD7):c.3082A>G



CATTGTCCACARTC

CARTCCCCAAC′]

CARTCCCCAAC′]


(p.Ile1028Val)



CCCAACTGGGAAAG










GGAATTCCG′]






NM_000483.4
−1

5099
[′TCAATGTTCCAGGT
5276
[′CCAGGTCTCTGG
5489
[′CCAGGTCTCTGG


(APOC2):c.1A>G



CTCTGGACACTRTG

ACACTRTGGGC′]

ACACTRTGGGC′]


(p.MetlVal)



GGCACACGACTCCT










CCCAGCTCT′]






NM_000391.3
1200
TPP1
5100
[′TGTCCCTCATGCCG
5277
[′CCGGCCTGGATT
5490
[′CCGGCCTGGATT


(TPP1):c.887-10A>G



GCCTGGATTTTYTTT

TTYTTTTTTTT′]

TTYTTTTTTTT′]






TTTTTTTTTTTTGAG










GGATGGG′]






NM_017890.4
157680
VPS13B
5101
[′CTTCTGCCCTGGGC
5278
[′CCTGGGCCCTGC
5491
[′CCTGGGCCCTGC


(VPS13B):c.8978A>G



CCTGCTTATCARTG

TTATCARTGAA′]

TTATCARTGAA′]


(p.Asn2993Ser)



AATCCAAATGGGAC










CTCTGGCTA′]






NM_000226.3
3857
KRT9
5102
[′GAGAAGAGCACCA
5279
[′CCATGCAGGAAC
5492
[′CCATGCAGGAAC


(KRT9):c.482A>G



TGCAGGAACTCADT

TCADTTCTCGG′]

TCADTTCTCGG′]


(p.Asn161Ser)



TCTCGGCTGGCCTCT










TACTTGGAT′]






NM_000529.2
4158
MC2R
5103
[′CCAAGTAACCCCT
5280-
[′CCCTACTGCGCC
5493-
[′CCCCTACTGCGC


(MC2R):c.761A>G



ACTGCGCCTGCTRC
5281
TGCTRCATGTC′,
5495
CTGCTRCATGT′,


(p.Tyr254Cys)



ATGTCTCTCTTCCAG

′CCTACTGCGCCTG

′CCCTACTGCGCCT






GTGAACGGC′]

CTRCATGTCT′]

GCTRCATGTC′,










′CCTACTGCGCCTG










CTRCATGTCT′]


NM_005957.4
4524
MTHFR
5104
[′CCAGGCCTCCACTT
5282
[′CCACTTCTACAC
5496
[′CCACTTCTACAC


(MTHFR):c.971A>G



CTACACCCTCARCC

CCTCARCCGCG′]

CCTCARCCGCG′]


(p.Asn324Ser)



GCGAGATGGCTACC










ACAGAGGTG′]






NM_000403.3
2582
GALE
5105
[′GGCTACTTGCCTGT
5283
[′CCTGTGGTCATC
5497
[′CCTGTGGTCATC


(GALE):c.101A>G



GGTCATCGATARCT

GATARCTTCCA′]

GATARCTTCCA′]


(p.Asn34Ser)



TCCATAATGCCTTCC










GTGGTGAG′]






NM_000356.3
6949
TCOF1
5106
[′CAGCCCGTAACCC
5284-
[′CCCTTCTGGACA
5498-
[′CCCTTCTGGACA


(TCOF1):c.149A>G



TTCTGGACATCTRTA
5285
TCTRTACACAC′,
5499
TCTRTACACAC′,


(p.Tyr50Cys)



CACACTGGCAACAG

′CCTTCTGGACATC

′CCTTCTGGACATC






TAAGTGGTG′]

TRTACACACT′]

TRTACACACT′]


NM_012464.4
7092
TLL1
5107
[′ACTTCTTACCAAAC
5286
[′CCAAACTTAACG
5500
[′CCAAACTTAACG


(TLL1):c.1885A>G



TTAACGGCACCRTA

GCACCRTAACC′]

GCACCRTAACC′]


(p.Ile629Val)



ACCACCCCTGGCTG










GCCCAAGGA′]






NM_000112.3
1836
SLC26A2
5108
[′GGAAATGTATGCC
5287
[′CCATTGGCTTTT
5501
[′CCATTGGCTTTT


(SLC26A2):c.1273A>G



ATTGGCTTTTGTRAT

GTRATATCATC′]

GTRATATCATC′]


(p.Asn425Asp)



ATCATCCCTTCCTTC










TTCCACTG′]






NM_000157.3
2629
GBA
5109
[′ACATCACCCACTTG
5288
[′CCACTTGGCTCA
5502
[′CCACTTGGCTCA


(GBA):c.680A>G



GCTCAAGACCARTG

AGACCARTGGA′]

AGACCARTGGA′]


(p.Asn227Ser)



GAGCGGTGAATGGG










AAGGGGTCA′]






NM_175073.2
54840
APTX
5110
[′GATAAATACCCAA
5289-
[′CCCAAAGGCCCG
5503-
[′CCCAAAGGCCCG


(APTX):c.602A>G



AGGCCCGTTACCRT
5290
TTACCRTTGGC′,
5504
TTACCRTTGGC′,


(p.His201Arg)



TGGCTGGTCTTACC

′CCAAAGGCCCGT

′CCAAAGGCCCGT






GTGGACCTCC′]

TACCRTTGGCT′]

TACCRTTGGCT′]


NM_020638.2
8074
FGF23
5111
[′TGGCGCACCCCAT
5291
[′CCCCATCAGACC
5505-
[′CCCCATCAGACC


(FGF23):c.211A>G



CAGACCATCTACRG

ATCTACRGTGA′]
5507
ATCTACRGTGA′,


(p.Ser71Gly)



TGAGTAGGGCTTCA



′CCCATCAGACCA






GGCTGGGAAG′]



TCTACRGTGAG′,










′CCATCAGACCAT










CTACRGTGAGT′]


NM_021102.3
10653
SPINT2
5112
[′AGGAACTCCTGCA
5292
[′CCTGCAATAACT
5508
[′CCTGCAATAACT


(SPINT2):c.488A>G



ATAACTTCATCTRTG

TCATCTRTGGA′]

TCATCTRTGGA′]


(p.Tyr163Cys)



GAGGCTGCCGGGGC










AATAAGAAC′]






NM_004795.3
9365
KL
5113
[′GTGCAGCCCGTGG
5293
[′CCGTGGTCACCC
5509
[′CCGTGGTCACCC


(KL):c.578A>G



TCACCCTGTACCRCT

TGTACCRCTGG′]

TGTACCRCTGG′]


(p.His193Arg)



GGGACCTGCCCCAG










CGCCTGCAG′]






NM_012193.3
−1

5114
[′GTTTTCCTACCCTG
5294-
[′CCCTGAGCGCCC
5510-
[′CCCTGAGCGCCC


(FZD4):c.766A>G



AGCGCCCCATCRTA
5295
CATCRTATTTC′,
5511
CATCRTATTTC′,


(p.Ile256Val)



TTTCTCAGTATGTGC

′CCTGAGCGCCCC

′CCTGAGCGCCCC






TATAATAT′]

ATCRTATTTCT′]

ATCRTATTTCT′]


NM_001099274.1
26277
TINF2
5115
[′ATGGGCCTCCACT
5296
[′CCACTAGGGGAG
5512
[′CCACTAGGGGAG


(TINF2):c.838A>G



AGGGGAGGCCATDA

GCCATDAGGAG′]

GCCATDAGGAG′]


(p.Lys280Glu)



GGAGCGCCCCACAG










TCATGCTGTT′]






NM_005682.6
9289
ADGRG1
5116
[′TCCTTCCCTGACCC
5297
[′CCCCAGGGGCCT
5513
[′CCCCAGGGGCCT


(ADGRG1):c.263A>G



CAGGGGCCTCTRCC

CTRCCACTTCT′]

CTRCCACTTCT′]


(p.Tyr88Cys)



ACTTCTGCCTCTACT










GGAACCGA′]






NM_000369.2
7253
TSHR
5117
[′CCGCAGTACAACC
5298
[′CCCAGGGGACAA
5514
[′CCCAGGGGACAA


(TSHR):c.1856A>G



CAGGGGACAAAGRT

AGRTACCAAAA′]

AGRTACCAAAA′]


(p.Asp619Gly)



ACCAAAATTGCCAA










GAGGATGGCT′]






NM_024009.2
2707
GJB3
5118
[′ATGCCGCGCCTGG
5299
[′CCTGGTGCAGTG
5515
[′CCTGGTGCAGTG


(GJB3):c.497A>G



TGCAGTGTGCCADC

TGCCADCGTGG′]

TGCCADCGTGG′]


(p.Asn166Ser)



GTGGCCCCCTGCCC










CAACATCGTG′]






NM_003722.4
8626
TP63
5119
[′TATCCGCGCCATGC
5300
[′CCATGCCTGTCT
5516
[′CCATGCCTGTCT


(TP63):c.697A>G



CTGTCTACAAARAA

ACAAARAAGCT′]

ACAAARAAGCT′]


(p.Lys233Glu)



GCTGAGCACGTCAC










GGAGGTGGT′]






NM_003494.3
8291
DYSF
5120
[′CAGCTCTTAACCAC
5301
[′CCACTCCAGCCA
5517
[′CCACTCCAGCCA


(DYSF):c.3443-33A>G



TCCAGCCACTCRCT

CTCRCTCTGGC′]

CTCRCTCTGGC′]






CTGGCACCTCTGTTT










TTTCCCTT′]






NM_003494.3
8291
DYSF
5121
[′AACTTGTCCCCTCC
5302
[′CCCCTCCCTGTG
5518-
[′CCCCTCCCTGTG


(DYSF):c.1285-2A>G



CTGTGTCTTCTRGCT

TCTTCTRGCTG′]
5520
TCTTCTRGCTG′,






GTGCAGCAAGATCT



′CCCTCCCTGTGTC






TGGAGAAG′]



TTCTRGCTGT′,










′CCTCCCTGTGTCT










TCTRGCTGTG′]


NM_002408.3
4247
MGAT2
5122
[′CTTATACTTTTCCT
5303
[′CCTAGAAGAGGA
5521
[′CCTAGAAGAGGA


(MGAT2):c.785A>G



AGAAGAGGATCRCT

TCRCTACTTAG′]

TCRCTACTTAG′]


(p.His262Arg)



ACTTAGCCCCAGAC










TTTTACCAT′]






NM_000492.3
1080
CFTR
5123
[′GTGATTATCACCA
5304
[′CCAGCACCAGTT
5522
[′CCAGCACCAGTT


(CFTR):c.2738A>G



GCACCAGTTCGTRT

CGTRTTATGTG′]

CGTRTTATGTG′]


(p.Tyr913Cys)



TATGTGTTTTACATT










TACGTGGGA′]






NM_001814.4
1075
CTSC
5124
[′TCTCAGACCCCAAT
5305
[′CCCCAATCCTAA
5523-
[′CCCCAATCCTAA


(CTSC):c.857A>G



CCTAAGCCCTCRGG

GCCCTCRGGAG′]
5525
GCCCTCRGGAG′,


(p.Gln286Arg)



AGGTTGTGTCTTGTA



′CCCAATCCTAAG






GCCAGTAT′]



CCCTCRGGAGG′,










′CCAATCCTAAGC










CCTCRGGAGGT′]


NM_005144.4
55806
HR
5125
[′TCCGACCCCTCCAA
5306
[′CCTCCAACCTGC
5526-
[′CCTCCAACCTGC


(HR):c.-218A>G



CCTGCGGCCCTRGA

GGCCCTRGAGC′]
5527
GGCCCTRGAGC′,






GCGCCCCCGCCGCC



′CCAACCTGCGGC






CCGGGGGAA′]



CCTRGAGCGCC′]


NM_018488.2
9496
TBX4
5126
[′TCCTTGTCCCGAGA
5307
[′CCCGAGAATCTT
5528-
[′CCCGAGAATCTT


(TBX4):c.1592A>G



ATCTTCCTTACRGTA

CCTTACRGTAC′]
5529
CCTTACRGTAC′,


(p.G1n531Arg)



CCATTCAGGAATGG



′CCGAGAATCTTCC






GGACTGTG′]



TTACRGTACC′]


NM_001089.2
21
ABCA3
5127
[′ACAGATCACCGTC
5308
[′CCGTCCTGCTGG
5530
[′CCGTCCTGCTGG


(ABCA3):c.1702A>G



CTGCTGGGCCACRA

GCCACRACGGT′]

GCCACRACGGT′]


(p.Asn568Asp)



CGGTGCCGGGAAGA










CCACCACCCT′]






NM_000525.3
37671
KCNJ1
5128
[′CTGGTGGCCCCGCT
5309-
[′CCCCGCTGATCA
5531-
[′CCCCGCTGATCA


(KCNDJ11):c.776A>G



GATCATCTACCRTG
5310
TCTACCRTGTC′,
5533
TCTACCRTGTC′,


(p.His259Arg)



TCATTGATGCCAAC

′CCCGCTGATCATC

′CCCGCTGATCATC






AGCCCACTC′]

TACCRTGTCA′]

TACCRTGTCA′,










′CCGCTGATCATCT










ACCRTGTCAT′]


NM_005587.2
4205
MEF2A
5129
[′TCTCCCCCTCCACC
5311
[′CCACCAGGTGGT
5534
[′CCACCAGGTGGT


(MEF2A):c.788A>G



AGGTGGTGGTARTC

GGTARTCTTGG′]

GGTARTCTTGG′]


(p.Asn263Ser)



TTGGAATGAACAGT










AGGAAACCA′]






NM_000098.2
1376
CPT2
5130
[′TTTTTAGGACCCTG
5312
[′CCTGGTTTGATA
5535-
[′CCCTGGTTTGAT


(CPT2):c.359A>G



GTTTGATATGTRCCT

TGTRCCTATCT′]
5536
ATGTRCCTATC′,


(p.Tyr120Cys)



ATCTGCTCGAGACT



′CCTGGTTTGATAT






CCGTTGTT′]



GTRCCTATCT′]


NM_178138.4
8022
LHX3
5131
[′GTGCGCCGCGCCC
5313-
[′CCCAGGACTTCG
5537-
[′CCCAGGACTTCG


(LHX3):c.332A>G



AGGACTTCGTGTRC
5314
TGTRCCACCTG′,
5538
TGTRCCACCTG′,


(p.Tyr111Cys)



CACCTGCACTGCTTT

′CCAGGACTTCGT

′CCAGGACTTCGT






GCCTGCGTC′]

GTRCCACCTGC′]

GTRCCACCTGC′]


NM_005502.3
19
ABCA1
5132
[′CAGATCACCTCCTT
5315
[′CCTCCTTCCTGG
5539-
[′CCTCCTTCCTGG


(ABCA1):c.2804A>G



CCTGGGCCACARTG

GCCACARTGGA′]
5540
GCCACARTGGA′,


(p.Asn935Ser)



GAGCGGGGAAGAC



′CCTTCCTGGGCCA






GACCACCATG′]



CARTGGAGCG′]


m.3260A>G
4567
MT-TL1
5133
[′GATGGCAGAGCCC
5316-
[′CCCGGTAATCGC
5541-
[′CCCGGTAATCGC






GGTAATCGCATARA
5317
ATARAACTTAA′,
5542
ATARAACTTAA′,






ACTTAAAACTTTAC

′CCGGTAATCGCA

′CCGGTAATCGCA






AGTCAGAGGT′]

TARAACTTAAA′]

TARAACTTAAA′]


m.4269A>G
4565
MT-TI
5134
[′GCATTCCCCCTCAA
5318-
[′CCCTCAAACCTA
5543-
[′CCCTCAAACCTA






ACCTAAGAAATRTG
5319
AGAAATRTGTC′,
5544
AGAAATRTGTC′,






TCTGATAAAAGAGT

′CCTCAAACCTAA

′CCTCAAACCTAA






TACTTTGAT′]

GAAATRTGTCT′]

GAAATRTGTCT′]


m.14495A>G
4541
MT-
5135
[′TCCAAAGACAACC
5320
[′CCATCATTCCCC
5545
[′CCATCATTCCCC




ND6

ATCATTCCCCCTRA

CTRAATAAATT′]

CTRAATAAATT′]






ATAAATTAAAAAAA










CTATTAAACC′]






NM_002764.3
5631
PRPS1
5136
[′CCAATCTCAGCCA
5321
[′CCAAGCTTGTTG
5546
[′CCAAGCTTGTTG


(PRPS1):c.341A>G



AGCTTGTTGCAART

CAARTATGCTA′]

CAARTATGCTA′]


(p.Asn114Ser)



ATGCTATCTGTAGC










AGGTGCAGAT′]






NM_000054.4
554
AVPR2
5137
[′GCGGAGCCCTGGG
5322
[′CCTGGGGCCGTC
5547
[′CCTGGGGCCGTC


(AVPR2):c.614A>G



GCCGTCGCACCTRT

GCACCTRTGTC′]

GCACCTRTGTC′]


(p.Tyr205Cys)



GTCACCTGGATTGC










CCTGATGGTG′]






NM_000033.3
215
ABCD1
5138
[′ATCGCCCTCCCTGC
5323-
[′CCCTGCTACCTT
5548-
[′CCCTGCTACCTT


(ABCD1):c.443A>G



TACCTTCGTCARCA
5324
CGTCARCAGTG′,
5549
CGTCARCAGTG′,


(p.Asn148Ser)



GTGCCATCCGTTAC

′CCTGCTACCTTCG

′CCTGCTACCTTCG






CTGGAGGGC′]

TCARCAGTGC′]

TCARCAGTGC′]


NM_000061.2
695
BTK
5139
[′AGCACCATCCCTG
5325-
[′CCCTGAGCTCAT
5550-
[′CCCTGAGCTCAT


(BTK):c.1082A>G



AGCTCATTAACTRC
5326
TAACTRCCATC′,
5551
TAACTRCCATC′,


(p.Tyr361Cys)



CATCAGCACAACTC

′CCTGAGCTCATTA

′CCTGAGCTCATTA






TGCAGGTGAG′]

ACTRCCATCA′]

ACTRCCATCA′]


NM_003413.3
7547
ZIC3
5140
[′CTACACGCACCCG
5327
[′CCGAGCTCCCTG
5552-
[′CCCGAGCTCCCT


(ZIC3):c.1213A>G



AGCTCCCTGCGCRA

CGCRAACACAT′]
5553
GCGCRAACACA′,


(p.Lys405Glu)



ACACATGAAGGTAA



′CCGAGCTCCCTGC






TTACCTCTTT′]



GCRAACACAT′]


NM_005448.2
9210
BMP15
5141
[′TTGGACATTGCCTT
5328
[′CCTTCTTGTTACT
5554
[′CCTTCTTGTTACT


(BMP15):c.704A>G



CTTGTTACTCTRTTT

CTRTTTCAAT′]

CTRTTTCAAT′]


(p.Tyr235Cys)



CAATGATACTCATA










AAAGCATT′]






NM_001363.4
1736
DKC1
5142
[′ATTAATGACCACA
5329
[′CCACAGCGGTCA
5555
[′CCACAGCGGTCA


(DKC1):c.1069A>G



GCGGTCATCTCTRC

TCTCTRCCTGC′]

TCTCTRCCTGC′]


(p.Thr357Ala)



CTGCGACCATGGTA










TAGTAGCCAA′]






NM_000481.3
275
AMT
5143
[′CGCAGGACACCGC
5330
[′CCGCTCTATGAC
5556
[′CCGCTCTATGAC


(AMT):c.125A>G



TCTATGACTTCCRCC

TTCCRCCTGGC′]

TTCCRCCTGGC′]


(p.His42Arg)



TGGCCCACGGCGGG










AAAATGGTG′]






NM_003361.3
7369
UMOD
5144
[′TGCCACGCCCTGG
5331
[′CCTGGCCACATG
5557-
[′CCCTGGCCACAT


(UMOD):c.383A>G



CCACATGTGTCART

TGTCARTGTGG′]
5558
GTGTCARTGTG′,


(p.Asn128Ser)



GTGGTGGGCAGCTA



′CCTGGCCACATGT






CTTGTGCGTA′]



GTCARTGTGG′]


NM_001382.3
1798
DPAGT1
5145
[′TCTCTCCCCGCAGG
5332
[′CCGCAGGAATCC
5559
[′CCGCAGGAATCC


(DPAGT1):c.509A>G



AATCCTGTACTRTGT

TGTACTRTGTC′]

TGTACTRTGTC′]


(p.Tyr170Cys)



CTACATGGGGCTGC










TGGCAGTG′]






NM_001128177.1
7068
THRB
5146
[′CTGCCATGCCAGC
5333
[′CCAGCCGCTTCC
5560
[′CCAGCCGCTTCC


(THRB):c.1324A>G



CGCTTCCTGCACRT

TGCACRTGAAG′]

TGCACRTGAAG′]


(p.Met442Val)



GAAGGTGGAATGCC










CCACAGAACT′]






NM_000141.4
2263
FGFR2
5147
[′TGCCCAGCCCCAC
5334
[′CCCACATCCAGT
5561-
[′CCCCACATCCAG


(FGFR2):c.874A>G



ATCCAGTGGATCRA

GGATCRAGCAC′]
5563
TGGATCRAGCA′,


(p.Lys292Glu)



GCACGTGGAAAAGA



′CCCACATCCAGT






ACGGCAGTAA′]



GGATCRAGCAC′,










′CCACATCCAGTG










GATCRAGCACG′]


NM_000371.3
7276
TTR
5148
[′ACCATTGCCGCCCT
5335-
[′CCGCCCTGCTGA
5564-
[′CCGCCCTGCTGA


(TTR):c.401A>G



GCTGAGCCCCTRCT
5337
GCCCCTRCTCC′,
5566
GCCCCTRCTCC′,


(p.Tyr134Cys)



CCTATTCCACCACG

′CCCTGCTGAGCCC

′CCCTGCTGAGCCC






GCTGTCGTC′]

CTRCTCCTAT′,

CTRCTCCTAT′,








′CCTGCTGAGCCCC

′CCTGCTGAGCCCC








TRCTCCTATT′]

TRCTCCTATT′]


NM_000371.3
7276
TTR
5149
[′CGACTCCGGCCCC
5338
[′CCCCCGCCGCTA
5567-
[′CCCCCGCCGCTA


(TTR):c.379A>G



CGCCGCTACACCRT

CACCRTTGCCG′]
5569
CACCRTTGCCG′,


(p.Ile127Val)



TGCCGCCCTGCTGA



′CCCCGCCGCTAC






GCCCCTACTC′]



ACCRTTGCCGC′,










′CCCGCCGCTACA










CCRTTGCCGCC′]


NM_000174.4
2815
GP9
5150
[′ACCCGCCACCTTCT
5339
[′CCTTCTGCTGGC
5570
[′CCTTCTGCTGGC


(GP9):c.182A>G



GCTGGCCAACARCA

CAACARCAGCC′]

CAACARCAGCC′]


(p.Asn61Ser)



GCCTTCAGTCCGTG










CCCCCGGGA′]






NM_000222.2
3815
KIT
5151
[′ACGGGAAGCCCTC
5340-
[′CCCTCATGTCTG
5571-
[′CCCTCATGTCTG


(KIT):c.1924A>G



ATGTCTGAACTCRA
5341
AACTCRAAGTC′,
5572
AACTCRAAGTC′,


(p.Lys642Glu)



AGTCCTGAGTTACC

′CCTCATGTCTGAA

′CCTCATGTCTGAA






TTGGTAATCA′]

CTCRAAGTCC′]

CTCRAAGTCC′]


NM_000530.6
4359
MPZ
5152
[′TCCCCTCATTCCTC
5342
[′CCTCATAGATCT
5573
[′CCTCATAGATCT


(MPZ):c.242A>G



ATAGATCTTCCRCT

TCCRCTATGCC′]

TCCRCTATGCC′]


(p.His8lArg)



ATGCCAAGGGACAA










CCCTACATT′]






NM_000233.3
−1

5153
[′AAAATGGCAATCC
5343
[′CCTCATCTTCAC
5574
[′CCTCATCTTCAC


(LHCGR):c.1733A>G



TCATCTTCACCGRTT

CGRTTTCACCT′]

CGRTTTCACCT′]


(p.Asp578Gly)



TCACCTGCATGGCA










CCTATCTCT′]






NM_000421.3
−1

5154
[′CCGCCGCGTCCGC
5344
[′CCGCCGCCTCCG
5575
[′CCGCCGCCTCCG


(KRT10):c.1374-2A>G



CGCCTCCGGAACYA

GAACYAAACGG′]

GAACYAAACGG′]






AACGGGGTGAGGTC










ACATTCGGTT′]






NM_000422.2
3872
KRT17
5155
[′TGAGAAGGCCACC
5345
[′CCACCATGCAGA
5576-
[′CCACCATGCAGA


(KRT17):c.274A>G



ATGCAGAACCTCVA

ACCTCVATGAC′]
5577
ACCTCVATGAC′,


(p.Asn92Asp)



TGACCGCCTGGCCT



′CCATGCAGAACC






CCTACCTGGA′]



TCVATGACCGC′]


NM_000422.2
3872
KRT17
5156
[′GAGAAGGCCACCA
5346
[′CCACCATGCAGA
5578-
[′CCACCATGCAGA


(KRT17):c.275A>G



TGCAGAACCTCART

ACCTCARTGAC′]
5579
ACCTCARTGAC′,


(p.Asn92Ser)



GACCGCCTGGCCTC



′CCATGCAGAACC






CTACCTGGAC′]



TCARTGACCGC′]


NM_000823.3
2692
GHRHR
5157
[′TTGTCTTTCCTGCA
5347
[′CCTGCAGGCGTC
5580
[′CCTGCAGGCGTC


(GHRHR):c.985A>G



GGCGTCTCTCCRAG

TCTCCRAGTCG′]

TCTCCRAGTCG′]


(p.Lys329Glu)



TCGACACTTTTCCTG










ATCCCACT′]






NM_000407.4
−1

5158
[′GCCGGCCGCCCCG
5348-
[′CCCCGAGCGTGC
5581-
[′CCCCGAGCGTGC


(GP1BB):c.338A>G



AGCGTGCGCCCTDC
5349
GCCCTDCCGCG′,
5583
GCCCTDCCGCG′,


(p.Tyr113Cys)



CGCGACCTGCGTTG

′CCCGAGCGTGCG

′CCCGAGCGTGCG






CGTGGCGCCC′]

CCCTDCCGCGA′]

CCCTDCCGCGA′,










′CCGAGCGTGCGC










CCTDCCGCGAC′]


NM_001146040.1
2741
GLRA1
5159
[′CCTCCACCCCCACT
5350-
[′CCCCACTCTAGG
5584-
[′CCCCACTCTAGG


(GLRA1):c.920A>G



CTAGGTGTCCTVTGT
5351
TGTCCTVTGTG′,
5586
TGTCCTVTGTG′,


(p.Tyr307Cys)



GAAAGCCATTGACA

′CCCACTCTAGGTG

′CCCACTCTAGGTG






TTTGGATG′]

TCCTVTGTGA′]

TCCTVTGTGA′,










′CCACTCTAGGTGT










CCTVTGTGAA′]


NM_182925.4
2324
FLT4
5160
[′CGCCTCCCCGCACC
5352
[′CCGCACCCCAGT
5587
[′CCGCACCCCAGT


(FLT4):c.3104A>G



CCAGTGCATCCRCA

GCATCCRCAGA′]

GCATCCRCAGA′]


(p.His1035Arg)



GAGACCTGGCTGCT










CGGAACATT′]






NM_212482.1
2335
FN1
5161
[′ACCGGGCTGTCCC
5353-
[′CCCCTGGGGTCA
5588-
[′CCCCTGGGGTCA


(FN1):c.2918A>G



CTGGGGTCACCTRT
5354
CCTRTTACTTC′,
5589
CCTRTTACTTC′,


(p.Tyr973Cys)



TACTTCAAAGTCTTT

′CCCTGGGGTCAC

′CCCTGGGGTCAC






GCAGTGAGC′]

CTRTTACTTCA′]

CTRTTACTTCA′]


NM_000121.3
2057
EPOR
5162
[′GGCTTATCCGATG
5355
[′CCGATGGCCCCT
5590
[′CCGATGGCCCCT


(EPOR):c.1460A>G



GCCCCTACTCCARC

ACTCCARCCCT′]

ACTCCARCCCT′]


(p.Asn487Ser)



CCTTATGAGAACAG










CCTTATCCCA′]






NM_001735.2
727
C5
5163
[′CGTCTACCCCCTCA
5356-
[′CCCCTCACCCAA
5591-
[′CCCCTCACCCAA


(C5):c.1115A>G



CCCAATCTACCYTG
5357
TCTACCYTGAT′,
5593
TCTACCYTGAT′,


(p.Lys372Arg)



ATGGGATATGGAAT

′CCCTCACCCAATC

′CCCTCACCCAATC






CCCAGGCTT′]

TACCYTGATG′]

TACCYTGATG′,










′CCTCACCCAATCT










ACCYTGATGG′]


NM_001844.4
1280
COL2A1
5164
[′ACGGAAGGCTCCC
5358-
[′CCCAGAACATCA
5594-
[′CCCAGAACATCA


(COL2A1):c.4172A>G



AGAACATCACCTRC
5359
CCTRCCACTGC′,
5595
CCTRCCACTGC′,


(p.Tyr1391Cys)



CACTGCAAGAACAG

′CCAGAACATCAC

′CCAGAACATCAC






CATTGCCTAT′]

CTRCCACTGCA′]

CTRCCACTGCA′]


NM_001904.3
1499
CTNNB1
5165
[′CTCTGGAATCCATT
5360
[′CCATTCTGGTGC
5596
[′CCATTCTGGTGC


(CTNNB1):c.121A>G



CTGGTGCCACTNCC

CACTNCCACAG′]

CACTNCCACAG′]


(p.Thr41Ala)



ACAGCTCCTTCTCTG










AGTGGTAA′]






NM_000040.1
345
APOC3
5166
[′GGATTTGGACCCT
5361-
[′CCCTGAGGTCAG
5597-
[′CCCTGAGGTCAG


(APOC3):c.280A>G



GAGGTCAGACCARC
5362

5598
ACCARCTTCAG′,


(p.Thr94Ala)



TTCAGCCGTGGCTG

′CCTGAGGTCAGA

′CCTGAGGTCAGA






CCTGAGACCT′]

CCARCTTCAGC′]

CCARCTTCAGC′]


NM_000488.3
462
SERPINC1
5167
[′TGCAGAGCAATCC
5363
[′CCAGAGCGGCCA
5599
[′CCAGAGCGGCCA


(SERPINC1):c.655A>G



AGAGCGGCCATCRA

TCRACAAATGG′]

TCRACAAATGG′]






CAAATGGGTGTCCA






(p.Asn219Asp)



ATAAGACCGA′]






NM_001085.4
12
SERPINA3
5168
[′TACAGACACCCAG
5364
[′CCCAGAACATCT
5600-
[′CCCAGAACATCT


(SERPINA3):c.1240A>G



AACATCTTCTTCRTG

TCTTCRTGAGC′]
5601
TCTTCRTGAGC′,


(p.Met414Val)



AGCAAAGTCACCAA



′CCAGAACATCTTC






TCCCAAGCA′]



TTCRTGAGCA′]


NM_001145.4
−1

5169
[′CTTCCTGACCCAGC
5365
[′CCAGCACTATGA
5602-
[′CCCAGCACTATG


(ANG):c.121A>G



ACTATGATGCCRAA

TGCCRAACCAC′]
5603
ATGCCRAACCA′,


(p.Lys41Glu)



CCACAGGGCCGGGA



′CCAGCACTATGA






TGACAGATA′]



TGCCRAACCAC′]


NM_001100.3
58
ACTA1
5170
[′GAGGCCCCCCTCA
5366
[′CCTCAATCCCAA
5604-
[′CCCTCAATCCCA


(ACTA1):c.350A>G



ATCCCAAGGCCARC

GGCCARCCGCG′]
5605
AGGCCARCCGC′,


(p.Asn117Ser)



CGCGAGAAGATGAC



′CCTCAATCCCAA






CCAGATCATG′]



GGCCARCCGCG′]


NM_014053.3
28982
FLVCR1
5171
[′GATCTTCAGCCTGT
5367
[′CCTGTACTCGCT
5606
[′CCTGTACTCGCT


(FLVCR1):c.361A>G



ACTCGCTGGTCRAC

GGTCRACGCCT′]

GGTCRACGCCT′]


(p.Asn121Asp)



GCCTTTCAGTGGAT










CCAGTACAG′]






NM_000334.4
6329
SCN4A
5172
[′GAAGCAGGCCTTC
5368
[′CCTTCGACATCA
5607
[′CCTTCGACATCA


(SCN4A):c.4078A>G



GACATCACCATCRT

CCATCRTGATC′]

CCATCRTGATC′]


(p.Met1360Val)



GATCCTCATCTGCCT










CAACATGGT′]






NM_004519.3
3786
KCNQ3
5173
[′GAACCAAAGCCTG
5369
[′CCTGTTGGCTTA
5608
[′CCTGTTGGCTTA


(KCNQ3):c.1403A>G



TTGGCTTAAACART

AACARTAAAGA′]

AACARTAAAGA′]


(p.Asn468Ser)



AAAGAGCGTTTCCG










CACGGCCTTC′]






NM_007375.3
23435
TARDBP
5174
[′AATGCCGAACCTA
5370
[′CCTAAGCACAAT
5609
[′CCTAAGCACAAT


(TARDBP):c.800A>G



AGCACAATAGCART

AGCARTAGACA′]

AGCARTAGACA′]


(p.Asn267Ser)



AGACAGTTAGAAAG










AAGTGGAAGA′]






NM_032520.4
84572
GNPTG
5175
[′TGCTGCCCCTGCAT
5371
[′CCTGCATCCTCC
5610
[′CCTGCATCCTCC


(GNPTG):c.6102A>G



CCTCCACCTTCRGG

ACCTTCRGGGC′]

ACCTTCRGGGC′]






GCCATGAGAAGTTG










CTGAGGACA′]






NM_000495.4
1287
COL4A5
5176
[′AGAACTTCCATTG
5372
[′CCATTGATGGCT
5611
[′CCATTGATGGCT


(COL4A5):c.466-2A>G



ATGGCTTCTTTTRGG

TCTTTTRGGGT′]

TCTTTTRGGGT′]






GTGAACCAGGTAGT










ATAATTATG′]






NM_000495.4
12875
COMA
5177
[′TTGCTATCCTTTCT
5373
[′CCTTTCTTTATCT
5612
[′CCTTTCTTTATCT


(COL4A5):c.1340-2A>G



TTATCTTACTCRGGT

TACTCRGGTG′]

TACTCRGGTG′]






GATGAGATATGTGA










ACCAGGCC′]






NM_000060.3
686
BTD
5178
[′CTCATGAACCAGA
5374
[′CCAGAACCTTGA
5613
[′CCAGAACCTTGA


(BTD):c.278A>G



ACCTTGACATCTRT

CATCTRTGAAC′]

CATCTRTGAAC′]


(p.Tyr93Cys)



GAACAGCAAGTGAT










GACTGCAGCC′]






NM_000060.3
686
BTD
5179
[′CTTGTTGACCGCTA
5375
[′CCGCTACCGTAA
5614
[′CCGCTACCGTAA


(BTD):c.641A>G



CCGTAAACACARCC

ACACARCCTCT′]

ACACARCCTCT′]


(p.Asn214Ser)



TCTACTTTGAGGCA










GCATTCGAT′]






NM_000094.3
1294
COL7A1
5180
[′CAGCTGGCCCGAC
5376
[′CCCGACCTGGTG
5615-
[′CCCGACCTGGTG


(COL7A1):c.425A>G



CTGGTGTCCCCARG

TCCCCARGGTG′]
5616
TCCCCARGGTG′,


(p.Lys142Arg)



GTGATCCCTACCCC



′CCGACCTGGTGTC






TACCATGCCT′]



CCCARGGTGA′]


NM_005247.2
2248
FGF3
5181
[′GGGGCGCCCCGGC
5377-
[′CCCGGCGCCGCA
5617-
[′CCCGGCGCCGCA


(FGF3):c.146A>G



GCCGCAAGCTCTRC
5378
AGCTCTRCTGC′,
5618
AGCTCTRCTGC′,


(p.Tyr49Cys)



TGCGCCACGAAGTA

′CCGGCGCCGCAA

′CCGGCGCCGCAA






CCACCTCCAG′]

GCTCTRCTGCG′]

GCTCTRCTGCG′]


NM_000313.3
5627
PROS1
5182
[′TGTGAATGCCCCG
5379-
[′CCCGAAGGCTAC
5619-
[′CCCCGAAGGCTA


(PROS1):c.701A>G



AAGGCTACAGATRT
5380
AGATRTAATCT′,
5621
CAGATRTAATC′,


(p.Tyr234Cys)



AATCTCAAATCAAA

′CCGAAGGCTACA

′CCCGAAGGCTAC






GTCTTGTGAA′]

GATRTAATCTC′]

AGATRTAATCT′,










′CCGAAGGCTACA










GATRTAATCTC′]


NM_004612.3
7046
TGFBR1
5183
[′TTCTGCCACCTCTG
5381
[′CCTCTGTACAAA
5622
[′CCTCTGTACAAA


(TGFBR1):c.134A>G



TACAAAAGACARTT

AGACARTTTTA′]

AGACARTTTTA′]


(p.Asn45Ser)



TTACTTGTGTGACA










GATGGGCTC′]






m.608A>G
4558
MT-TF
5184
[′GTAGCTTACCTCCT
5382
[′CCTCCTCAAAGC
5623-
[′CCTCCTCAAAGC






CAAAGCAATACRCT

AATACRCTGAA′]
5624
AATACRCTGAA′,






GAAAATGTTTAGAC



′CCTCAAAGCAAT






GGGCTCACA′]



ACRCTGAAAAT′]


NM_001376.4
1778
DYNC1H1
5185
[′CTAAGAATAACCA
5383
[′CCAATCAGGTAA
5625
[′CCAATCAGGTAA


(DYNC1H1):c.2909A>G



ATCAGGTAATCTRC

TCTRCTTGAAT′]

TCTRCTTGAAT′]


(p.Tyr970Cys)



TTGAATCCACCAAT










TGAAGAGTGC′]






NM_000459.4
7010
TEK
5186
[′ATGCTCTCTTCCTT
5384
[′CCTTCCCTCCAG
5626
[′CCTTCCCTCCAG


(TEK):c.2690A>G



CCCTCCAGGCTVCT

GCTVCTTGTAC′]

GCTVCTTGTAC′]


(p.Tyr897Cys)



TGTACCTGGCCATT










GAGTACGCG′]






NM_014191.3
6334
SCN8A
5187
[′CATGTACATTGCCA
5385
[′CCATCATCCTGG
5627
[′CCATCATCCTGG


(SCN8A):c.5302A>G



TCATCCTGGAGRAC

AGRACTTCAGT′]

AGRACTTCAGT′]


(p.Asn1768Asp)



TTCAGTGTAGCCAC










AGAGGAAAG′]






NM_002552.4
5000
ORC4
5188
[′CATCATAAAAACC
5386
[′CCAAACACTTCT
5628
[′CCAAACACTTCT


(ORC4):c.521A>G



AAACACTTCTCTRT

CTRTAATCTTT′]

CTRTAATCTTT′]


(p.Tyr174Cys)



AATCTTTTTGACATT










TCTCAGTCT′]






NM_004813.2
9409
PEX16
5189
[′TACTTGCCCACCTG
5387-
[′CCACCTGGCAGA
5629-
[′CCACCTGGCAGA


(PEX16):c.992A>G



GCAGAAAATCTRCT
5388
AAATCTRCTTC′,
5630
AAATCTRCTTC′,


(p.Tyr331Cys)



TCTACAGTTGGGGC

′CCTGGCAGAAAA

′CCTGGCAGAAAA






TGACAGACC′]

TCTRCTTCTAC′]

TCTRCTTCTAC′]


NM_016952.4
50937
CDON
5190
[′GTTTTTGTTTTCCC
5389
[′CCCTCAAAGGTT
5631
[′CCCTCAAAGGTT


(CDON):c.2368A>G



TCAAAGGTTCARCA

CARCATACAAA′]

CARCATACAAA′]


(p.Thr790Ala)



TACAAATTTAGGGT










CATTGCCAT′]






NM_016464.4
51524
TMEM138
5191
[′TACTTTGCCCTCAG
5390-
[′CCCTCAGCATCT
5632-
[′CCCTCAGCATCT


(TMEM138):c.287A>G



CATCTCCCTTCRTGT
5391
CCCTTCRTGTC′,
5633
CCCTTCRTGTC′,


(p.His96Arg)



CTGGGTCATGGTAA

′CCTCAGCATCTCC

′CCTCAGCATCTCC






GAGTGGCA′]

CTTCRTGTCT′]

CTTCRTGTCT′]


NM_005022.3
5216
PFN1
5192
[′GTTGATCAAACCA
5392
[′CCACCGTGGACA
5634
[′CCACCGTGGACA


(PFN1):c.350A>G



CCGTGGACACCTYC

CCTYCTTTGCC′]

CCTYCTTTGCC′]


(p.Glu117Gly)



TTTGCCCATCAGCA










GGACTAGCGC′]






NM_022787.3
64802
NMNAT1
5193
[′GGTCATCCTGGCCC
5393
[′CCCCTTTGCAGA
5635
[′CCCCTTTGCAGA


(NMNAT1):c.817A>G



CTTTGCAGAGARAC

GARACACTGCA′]

GARACACTGCA′]


(p.Asn273Asp)



ACTGCAGAAGCTAA










GACATAGGA′]






NM_005340.6
3094
HINT1
5194
[′GACATTTCCCCTCA
5394-
[′CCCCTCAAGCAC
5636-
[′CCCCTCAAGCAC


(HINT1):c.152A>G



AGCACCAACACRTT
5396
CAACACRTTTT′,
5638
CAACACRTTTT′,


(p.His5lArg)



TTCTGGTGATACCC

′CCCTCAAGCACC

′CCCTCAAGCACC






AAGAAACAT′]

AACACRTTTTC′,

AACACRTTTTC′,








′CCTCAAGCACCA

′CCTCAAGCACCA








ACACRTTTTCT′]

ACACRTTTTCT′]


NM_005211.3
1436
CSF1R
5195
[′GACTAACCCTGCA
5397
[′CCTGCAGTGCTT
5639
[′CCTGCAGTGCTT


(CSF1R):c.2320-2A>G



GTGCTTTCCCTCRGT

TCCCTCRGTGC′]

TCCCTCRGTGC′]






GCATCCACCGGGAC










GTGGCAGCG′]






NM_001039958.1
145873
MESP2
5196
[′GCGGCAGAGCGCC
5398
[′CCAGCGAGCGGG
5640
[′CCAGCGAGCGGG


(MESP2):c.271A>G



AGCGAGCGGGAGRA

AGRAACTGCGC′]

AGRAACTGCGC′]


(p.Lys91Glu)



ACTGCGCATGCGCA










CGCTGGCCCG′]






NM_001099274.1
26277
TINF2
5197
[′TAGGGGAGGCCAT
5399
[′CCATAAGGAGCG
5641
[′CCATAAGGAGCG


(TINF2):c.850A>G



AAGGAGCGCCCCRC

CCCCRCAGTCA′]

CCCCRCAGTCA′]


(p.Thr284Ala)



AGTCATGCTGTTTCC










CTTTAGGAA′]






NM_003863.3
8818
DPM2
5198
[′GCCGTTAGCCTGAT
5400
[′CCTGATCATCTT
5642
[′CCTGATCATCTT


(DPM2):c.68A>G



CATCTTCACCTRCTA

CACCTRCTACA′]

CACCTRCTACA′]


(p.Tyr23Cys)



CACCGCCTGGGTGA










TTCTCTTG′]






NM_000530.6
4359
MPZ
5199
[′AAGGATGGCTCCA
5401
[′CCATTGTCATAC
5643
[′CCATTGTCATAC


(MPZ):c.347A>G



TTGTCATACACARC

ACARCCTAGAC′]

ACARCCTAGAC′]


(p.Asn116Ser)



CTAGACTACAGTGA










CAATGGCACG′]






NM_000138.4
2200
FBN1
5200
[′ACCCGGATTTGCC
5402
[′CCACAAAAGAA
5644
[′CCACAAAAGAA


(FBN1):c.3058A>G



ACAAAAGAAATTRC

ATTRCAAATGGA′]

ATTRCAAATGGA′]


(p.Thr1020Ala)



AAATGGAAAGCCTT










TCTTCAAAGG′]






NM_000169.2
−1

5201
[′GGCCTGTAATCCTG
5403
[′CCTGCCTGCTTC
5645
[′CCTGCCTGCTTC


(GLA):c.1153A>G



CCTGCTTCATCRCAC

ATCRCACAGCT′]

ATCRCACAGCT′]


(p.Thr385Ala)



AGCTCCTCCCTGTG










AAAAGGAA′]






NM_000257.3
4625
MYH7
5202
[′AGCGGCCATCCCT
5404
[′CCCTGAGGGACA
5646-
[′CCCTGAGGGACA


(MYH7):c.2206A>G



GAGGGACAGTTCRT

GTTCRTTGATA′]
5647
GTTCRTTGATA′,


(p.Ile736Val)



TGATAGCAGGAAGG



′CCTGAGGGACAG






GGGCAGAGAA′]



TTCRTTGATAG′]


NM_018972.2
54332
GDAP1
5203
[′AGCATGTATTACCC
5405
[′CCCACGGGTACA
5648
[′CCCACGGGTACA


(GDAP1):c.368A>G



ACGGGTACAACRTT

ACRTTACCGAG′]

ACRTTACCGAG′]


(p.His123Arg)



ACCGAGAGCTGCTT










GACTCCTTG′]






NM_001946.3
1848
DUSP6
5204
[′ACTACCATCCGAG
5406
[′CCGAGTCTGTTG
5649
[′CCGAGTCTGTTG


(DUSP6):c.566A>G



TCTGTTGCACTAYTG

CACTAYTGGGG′]

CACTAYTGGGG′]


(p.Asn189Ser)



GGGTCTCGGTCAAG










GTCAGACTC′]






NM_003867.3
8822
FGF17
5205
[′TACCAAGGCCAGC
5407
[′CCAGCTGCCCTT
5650
[′CCAGCTGCCCTT


(FGF17):c.560A>G



TGCCCTTCCCCARCC

CCCCARCCACG′]

CCCCARCCACG′]


(p.Asn187Ser)



ACGCCGAGAAGCAG










AAGCAGTTC′]






NM_015560.2
4976
OPA1
5206
[′TTTTTATTTTTCCT
5408
[′CCTGAGTAGACC
5651
[′CCTGAGTAGACC


(OPA1):c.1146A>G



GAGTAGACCATRTC

ATRTCCTTAAA′]

ATRTCCTTAAA′]


(p.Ile382Met)



CTTAAATGTAAAAG










GCCCTGGAC′]






NM_002972.3
6305
SBF1
5207
[′AAGGCCATGCCCT
5409
[′CCCTCCAGCACC
5652-
[′CCCTCCAGCACC


(SBF1):c.1249A>G



CCAGCACCTTCAYC

TTCAYCAGGAA′]
5653
TTCAYCAGGAA′,


(p.Met417Val)



AGGAAATCGTCCTC



′CCTCCAGCACCTT






TACCAGCCCA′]



CAYCAGGAAA′]


NM_006876.2
11041
B4GAT1
5208
[′GTTCCATCCCCAAA
5410
[′CCAAAAGGAGG
5654-
[′CCCCAAAAGGAG


(B4GAT1):c.1168A>G



AGGAGGCTGAARAT

CTGAARATCAGC′]
5656
GCTGAARATCA′,


(p.Asn390Asp)



CAGCACAATAAGAT



′CCCAAAAGGAGG






CCTATATCG′]



CTGAARATCAG′,










′CCAAAAGGAGGC










TGAARATCAGC′]


NM_000218.2
3784
KCNQ1
5209
[′CGCACCCACGTCC
5411
[′CCAGGGCCGCGT
5657
[′CCAGGGCCGCGT


(KCNQ1):c.332A>G



AGGGCCGCGTCTRC

CTRCAACTTCC′]

CTRCAACTTCC′]


(p.Tyr111Cys)



AACTTCCTCGAGCG










TCCCACCGGC′]






NM_000492.3
1080
CFTR
5210
[′CAGGGACCCCAGC
5412
[′CCAGCGCCCGAG
5658-
[′CCCAGCGCCCGA


(CFTR):c.1A>G



GCCCGAGAGACCRT

AGACCRTGCAG′]
5659
GAGACCRTGCA′,


(p.MetlVal)



GCAGAGGTCGCCTC



′CCAGCGCCCGAG






TGGAAAAGGC′]



AGACCRTGCAG′]


NM_007294.3
672
BRCA1
5211
[′GAACCTGTCTCCAC
5413
[′CCACAAAGTGTG
5660
[′CCACAAAGTGTG


(BRCA1):c.122A>G



AAAGTGTGACCRCA

ACCRCATATTT′]

ACCRCATATTT′]


(p.His41Arg)



TATTTTGCAAGTAA










GTTTGAATG′]






NM_007294.3
672
BRCA1
5212
[′GTTTTCTCCTTCCA
5414
[′CCTTCCATTTATC
5661-
[′CCTTCCATTTATC


(BRCA1):c.44852A>G



TTTATCTTTCTRGGT

TTTCTRGGTC′]
5662
TTTCTRGGTC′,






CATCCCCTTCTAAAT



′CCATTTATCTTTC






GCCCATC′]



TRGGTCATCC′]


NM_014795.3
9839
ZEB2
5213
[′AAACACAAGCACC
5415
[′CCACCTTATCGA
5663
[′CCACCTTATCGA


(ZEB2):c.3134A>G



ACCTTATCGAGCRC

GCRCTCAAGGC′]

GCRCTCAAGGC′]


(p.His1045Arg)



TCAAGGCTTCACTC










GGGCGAGAAG′]






NM_001287.5
1186
CLCN7
5214
[′TGTCCCGGCCTGCA
5416
[′CCTGCAGAGCTT
5664
[′CCTGCAGAGCTT


(CLCN7):c.296A>G



GAGCTTGGACTRTG

GGACTRTGACA′]

GGACTRTGACA′]


(p.Tyr99Cys)



ACAACAGTGAGAAC










CAGCTGTTC′]






NM_080605.3
126792
B3GALT6
5215
[′CGCCACGCCCGCC
5417
[′CCCGCCGCAGCA
5665-
[′CCCGCCGCAGCA


(B3GALT6):c.1A>G



GCAGCAGCTTCAYG

GCTTCAYGGCG′]
5667
GCTTCAYGGCG′,


(p.MetlVal)



GCGCCCGCGCCGGG



′CCGCCGCAGCAG






CCGGCGGCCC′]



CTTCAYGGCGC′,










′CCGCAGCAGCTT










CAYGGCGCCCG′]


NM_000207.2
−1

5216
[′TCCTGCACCGAGA
5418
[′CCGAGAGAGATG
5668
[′CCGAGAGAGATG


(1NS):c.*59A>G



GAGATGGAATAARG

GAATAARGCCC′]

GAATAARGCCC′]






CCCTTGAACCAGCC










CTGCTGTGCC′]






NM_000784.3
1593
CYP27A1
5217
[′TGGGCCCTGTACC
5419
[′CCACCTCTCAAA
5669
[′CCACCTCTCAAA


(CYP27A1):c.1061A>G



ACCTCTCAAAGGRC

GGRCCCTGAGA′]

GGRCCCTGAGA′]


(p.Asp354Gly)



CCTGAGATCCAGGA










GGCCTTGCAC′]






NM_000540.2
6261
RYR1
5218
[′CTACCTGTACACCG
5420
[′CCGTGGTGGCCT
5670
[′CCGTGGTGGCCT


(RYRO:c.14572A>G



TGGTGGCCTTCRAC

TCRACTTCTTC′]

TCRACTTCTTC′]


(p.Asn4858Asp)



TTCTTCCGCAAGTTC










TACAACAA′]






NM_000238.3
3757
KCNH2
5219
[′CACCCCGGCCGCA
5421
[′CCGCATCGCCGT
5671
[′CCGCATCGCCGT


(KCNH2):c.1478A>G



TCGCCGTCCACTNC

CCACTNCTTCA′]

CCACTNCTTCA′]


(p.Tyr493Cys)



TTCAAGGGCTGGTT










CCTCATCGAC′]






NM_000335.4
6331
SCN5A
5220
[′CCGAGTCCTCCGG
5422
[′CCGGGCCCTGAA
5672
[′CCGGGCCCTGAA


(SCN5A):c.688A>G



GCCCTGAAAACTRT

AACTRTATCAG′]

AACTRTATCAG′]


(p.Ile230Val)



ATCAGTCATTTCAG










GTGAAAATCA′]






NM_000169.2
−1

5221
[′TATTTTACCCATTG
5423
[′CCCATTGTTTTCT
5673-
[′CCCATTGTTTTCT


(GLA):c.548-2A>G



TTTTCTCATACRGGT

CATACRGGTT′]
5674
CATACRGGTT′,






TATAAGCACATGTC



′CCATTGTTTTCTC






CTTGGCCC′]



ATACRGGTTA′]


NM_000146.3
2512
FTL
5222
[′GTTAGCTCCTTCTT
5424
[′CCTTCTTGCCAA
5675
[′CCTTCTTGCCAA


(FTL):c.1A>G



GCCAACCAACCRTG

CCAACCRTGAG′]

CCAACCRTGAG′]


(p.MetlVal)



AGCTCCCAGATTCG










TCAGAATTA′]






NM_000531.5
5009
OTC
5223
[′GTCATGGTGTCCCT
5425-
[′CCCTGCTGACAG
5676-
[′CCCTGCTGACAG


(OTC):c.1034A>G



GCTGACAGATTRCT
5426
ATTRCTCACCT′,
5677
ATTRCTCACCT′,


(p.Tyr345Cys)



CACCTCAGCTCCAG

′CCTGCTGACAGA

′CCTGCTGACAGA






AAGCCTAAA′]

TTRCTCACCTC′]

TTRCTCACCTC′]


NM_000531.5
5009
OTC
5224
[′TGTTTTCTTACCAC
5427
[′CCACACAAGATA
5678
[′CCACACAAGATA


(OTC):c.350A>G



ACAAGATATTCDTT

TTCDTTTGGGT′]

TTCDTTTGGGT′]


(p.His117Arg)



TGGGTGTGAATGAA










AGTCTCACG′]






NM_000531.5
5009
OTC
5225
[′TACCATCCTATCCA
5428
[′CCAGATCCTGGC
5679
[′CCAGATCCTGGC


(OTC):c.524A>G



GATCCTGGCTGDTT

TGDTTACCTCA′]

TGDTTACCTCA′]


(p.Asp175Gly)



ACCTCACGCTCCAG










GTTGGTTTA′]






NM_000531.5
5009
OTC
5226
[′CATCCTATCCAGAT
5429
[′CCAGATCCTGGC
5680
[′CCAGATCCTGGC


(OTC):c.527A>G



CCTGGCTGATTRCCT

TGATTRCCTCA′]

TGATTRCCTCA′]


(p.Tyr176Cys)



CACGCTCCAGGTTG










GTTTATTT′]






NM_000531.5
5009
OTC
5227
[′TCTCCTTCATCCCG
5430
[′CCGTGCCTTTTA
5681-
[′CCCGTGCCTTTT


(OTC):c.542A>G



TGCCTTTTAGGRAC

GGRACACTATA′]
5682
AGGRACACTAT′,


(p.Glu181Gly)



ACTATAGCTCTCTG



′CCGTGCCTTTTAG






AAAGGTCTT′]



GRACACTATA′]


NM_024301.4
79147
FKRP
5228
[′CCAGCTAGCCCCA
5431
[′CCCCAGACTTCG
5683-
[′CCCCAGACTTCG


(FKRP):c.1A>G



GACTTCGGCCCCRT

GCCCCRTGCGG′]
5685
GCCCCRTGCGG′,


(p.MetlVal)



GCGGCTCACCCGCT



′CCCAGACTTCGG






GCCAGGCTGC′]



CCCCRTGCGGC′,










′CCAGACTTCGGC










CCCRTGCGGCT′]


NM_000321.2
5925
RB1
5229
[′AGCCTTCCAGACC
5432
[′CCCAGAAGCCAT
5686
[′CCCAGAAGCCAT


(RBO:c.1927A>G



CAGAAGCCATTGRA

TGRAATCTACC′]

TGRAATCTACC′]


(p.Lys643Glu)



ATCTACCTCTCTTTC










ACTGTTTTA′]






NM_015713.4
50484
RRM2B
5230
[′AAAAGATCCTGAG
5433
[′CCTGAGAAGAAA
5687
[′CCTGAGAAGAAA


(RRM2B):c.581A>



AAGAAAACTCCTYC

ACTCCTYCTAC′]

ACTCCTYCTAC′]


G(p.Glu194Gly)



TACAGCAGCAAAGG










CCACCACTCT′]






NM_000219.5
3753
KCNE1
5231
[′CACTCGAACGACC
5434
[′CCCATTCAACGT
5688
[′CCCATTCAACGT


(KCNE1):c.242A>G



CATTCAACGTCTDC

CTDCATCGAGT′]

CTDCATCGAGT′]


(p.Tyr81Cys)



ATCGAGTCCGATGC










CTGGCAAGAG′]






NM_003108.3
6664
SOX11
5232
[′AAGCACATGGCCG
5435
[′CCGACTACCCCG
5689
[′CCGACTACCCCG


(SOX11):c.347A>G



ACTACCCCGACTRC

ACTRCAAGTAC′]

ACTRCAAGTAC′]


(p.Tyr116Cys)



AAGTACCGGCCCCG










GAAAAAGCCC′]






NM_002764.3
5631
PRPS1
5233
[′AATCTCAGCCAAG
5436
[′CCAAGCTTGTTG
5690
[′CCAAGCTTGTTG


(PRPSO:c.343A>G



CTTGTTGCAAATRTG

CAAATRTGCTA′]

CAAATRTGCTA′]


(p.Met115Val)



CTATCTGTAGCAGG










TGCAGATCA′]






NM_000546.5
7157
TP53
5234
[′TCTCCTCCCTGCTT
5437
[′CCTGCTTCTGTCT
5691
[′CCTGCTTCTGTCT


(TP53):c.1101-2A>G



CTGTCTCCTACRGCC

CCTACRGCCA′]

CCTACRGCCA′]






ACCTGAAGTCCAAA










AAGGGTCA′]






NM_000166.5
2705
GJB1
5235
[′CGAGAAAACCGTC
5438
[′CCGTCTTCACCG
5692
[′CCGTCTTCACCG


(GJB1):c.580A>G



TTCACCGTCTTCRTG

TCTTCRTGCTA′]

TCTTCRTGCTA′]


(p.Met194Val)



CTAGCTGCCTCTGG










CATCTGCAT′]






NM_003159.2
6792
CDKL5
5236
[′TTAATCAGCCACA
5439
[′CCACAATGATGT
5693
[′CCACAATGATGT


(CDKL5):c.449A>G



ATGATGTCCTAARA

CCTAARACTGT′]

CCTAARACTGT′]


(p.Lys150Arg)



CTGTGTGACTTTGGT










AAGTTAAAA′]






NM_000053.3
540
ATP7B
5237
[′ATCCAGACCACCTT
5440
[′CCACCTTCATAG
5694-
[′CCACCTTCATAG


(ATP7B):c.122A>G



CATAGCCAACAYTG

CCAACAYTGTC′]
5695
CCAACAYTGTC′,


(p.Asn41Ser)



TCAAAAGCAAAACT



′CCTTCATAGCCAA






CTTCTTCAT′]



CAYTGTCAAA′]


NM_006306.3
8243
SMC1A
5238
[′GTGGCTACCAACA
5441
[′CCAACATTGATG
5696
[′CCAACATTGATG


(SMC1A):c.3254A>G



TTGATGAGATCTRT

AGATCTRTAAG′]

AGATCTRTAAG′]


(p.Tyr1085Cys)



AAGGCCCTGTCCCG










CAATAGCAGT′]






NM_005154.4
9101
USP8
5239
[′GAACCTTCCAAAC
5442
[′CCAAACTGAAGC
5697
[′CCAAACTGAAGC


(USP8):c.2150A>G



TGAAGCGCTCCTDC

GCTCCTDCTCC′]

GCTCCTDCTCC′]


(p.Tyr717Cys)



TCCTCCCCAGATAT










AACCCAGGCT′]






NM_000117.2
2010
EMD
5240
[′TCTGCTACCGCTGC
5443
[′CCGCTGCCCCCC
5698
[′CCGCTGCCCCCC


(EMD):c.266-2A>G



CCCCCTTCCCARGG

TTCCCARGGCT′]

TTCCCARGGCT′]






CTACAATGACGACT










ACTATGAAG′]






NM_207352.3
285440
CYP4V2
5241
[′CTACGTGCCCTTCT
5444
[′CCCTTCTCTGCT
5699-
[′CCCTTCTCTGCT


(CYP4V2):c.1393A>G



CTGCTGGCCCCRGG

GGCCCCRGGAA′]
5700
GGCCCCRGGAA′,


(p.Arg465Gly)



AACTGTATAGGTTT



′CCTTCTCTGCTGG






GTATCCATC′]



CCCCRGGAAC′]


NM_000546.5
7157
TP53
5242
[′CTGTACCACCATCC
5445
[′CCATCCACTACA
5701
[′CCATCCACTACA


(TP53):c.709A>G



ACTACAACTACRTG

ACTACRTGTGT′]

ACTACRTGTGT′]


(p.Met237Val)



TGTAACAGTTCCTG










CATGGGCGG′]






NM_016069.9
−1

5243
[′CTCACCCGTCCCCT
5446
[′CCTCTCCTCTGC
5702-
[′CCCCTCTCCTCT


(PAM16):c.226A>G



CTCCTCTGCAGRAC

AGRACTATGAA′]
5704
GCAGRACTATG′,


(p.Asn76Asp)



TATGAACACTTATTT



′CCCTCTCCTCTGC






AAGGTGAA′]



AGRACTATGA′,










′CCTCTCCTCTGCA










GRACTATGAA′]


NM_006785.3
10892
MALT1
5244
[′AACACCCCCTTTCT
5447
[′CCTTTCTTTTTTT
5705
[′CCTTTCTTTTTTT


(MALT1):c.1019-2A>G



TTTTTTTTCAARGCG

TTCAARGCGA′]

TTCAARGCGA′]






AAGGACAAGGTTGC










CCTTTTGA′]






NM_004771.3
9313
MMP20
5245
[′GGAGAAGGCCTGG
5448
[′CCTGGGAGGAGA
5706
[′CCTGGGAGGAGA


(MMP20):c.611A>G



GAGGAGATACACRT

TACACRTTTCG′]

TACACRTTTCG′]


(p.His204Arg)



TTCGACAATGCTGA










GAAGTGGACT′]






NM_003159.2
6792
CDKL5
5246
[′CACAATGATGTCCT
5449
[′CCTAAAACTGTG
5707
[′CCTAAAACTGTG


(CDKL5):c.458A>G



AAAACTGTGTGRCT

TGRCTTTGGTA′]

TGRCTTTGGTA′]


(p.Asp153Gly)



TTGGTAAGTTAAAA










AGAAATTAA′]






NM_001204830.1
−1

5247
[′CCGGACTACTGCCT
5450
[′CCTATCACCATT
5708
[′CCTATCACCATT


(LIPT1):c.535A>G



ATCACCATTGCRCTT

GCRCTTTATTA′]

GCRCTTTATTA′]


(p.Thr179Ala)



TATTATGTAGTACTG










ATGGGAC′]






NM_000921.4
5139
PDE3A
5248
[′AGTTTCTTCCACTT
5451
[′CCACTTGGACCA
5709
[′CCACTTGGACCA


(PDE3A):c.1333A>G



GGACCACCACCRCC

CCACCRCCTCG′]

CCACCRCCTCG′]


(p.Thr445Ala)



TCGGCCACAGGTCT










ACCCACCTT′]






NM_000182.4
3030
HADHA
5249
[′TTGCTCAATTCCAG
5452
[′CCAGTCTTTACC
5710
[′CCAGTCTTTACC


(HADHA):c.9192A>G



TCTTTACCACCYAA

ACCYAAAAAAC′]

ACCYAAAAAAC′]






AAAACATATAAAGC










ACTTGCTCA′]






NM_000169.2
−1

5250
[′GTGTACTCCTGTGA
5453
[′CCTGTGAGTGGC
5711
[′CCTGTGAGTGGC


(GLA):c.620A>G



GTGGCCTCTTTRTAT

CTCTTTRTATG′]

CTCTTTRTATG′]


(p.Tyr207Cys)



GTGGCCCTTTCAAA










AGGTGAGA′]






NM_000238.3
3757
KCNH2
5251
[′TGGTCCAGCCTGG
5454
[′CCTGGAGATCAC
5712
[′CCTGGAGATCAC


(KCNH2):c.2582A>G



AGATCACCTTCANC

CTTCANCCTGC′]

CTTCANCCTGC′]


(p.Asn861Ser)



CTGCGAGATGTGAG










TTGGCTGCCC′]






NM_000218.2
3784
KCNQ1
5252
[′GCTCCCCCTCTCCT
5455
[′CCTGCACTCCAC
5713
[′CCTGCACTCCAC


(KCNQ1):c.605A>G



GCACTCCACAGRCC

AGRCCTCATCG′]

AGRCCTCATCG′]


(p.Asp202Gly)



TCATCGTGGTCGTG










GCCTCCATG′]






NM_012203.1
9380
GRHPR
5253
[′CACCATGTCCTTGT
5456
[′CCTTGTTGGCAG
5714
[′CCTTGTTGGCAG


(GRHPR):c.934A>G



TGGCAGCTAACRAC

CTAACRACTTG′]

CTAACRACTTG′]


(p.Asn312Asp)



TTGCTGGCTGGCCT










GAGAGGGGA′]






NM_021007.2
6326
SCN2A
5254
[′ACTTTGTCTTCCTT
5457
[′CCTTGACGATAT
5715
[′CCTTGACGATAT


(SCN2A):c.3872A>G



GACGATATTCTRCTT

TCTRCTTTATT′]

TCTRCTTTATT′]






TATTCAATATGCTCA










TTATGTG′]






NM_002693.2
8542
POLG
5255
[′GTGGGCATCAGCC
5458
[′CCGTGAGCATGC
5716
[′CCGTGAGCATGC


(POLG):c.2840A>G



GTGAGCATGCCARA

CARAATCTTCA′]

CARAATCTTCA′]


(p.Lys947Arg)



ATCTTCAACTACGG










CCGCATCTAT′]






NM_020533.2
57192
MCOLN1
5256
[′TCTGAGTGCCTGTT
5459
[′CCTGTTCTCGCT
5717
[′CCTGTTCTCGCT


(MCOLN1):c.1406A>G



CTCGCTCATCARTG

CATCARTGGGG′]

CATCARTGGGG′]


(p.Asn469Ser)



GGGACGACATGTTT










GTGACGTTC′]






NM_000069.2
779
CACNA1S
5257
[′TCGCTTTCCCATCC
5460
[′CCCATCCTTTTCC
5718-
[′CCCATCCTTTTCC


(CACNA1S):c.3526-2A>G



TTTTCCTTCCCRGGG

TTCCCRGGGC′]
5719
TTCCCRGGGC′,








CTACTTTGGAGACC

′CCATCCTTTTCCT








CCTGGAAT′]

TCCCRGGGCT′]


NM_017662.4
140803
TRPM6
5258
[′CAAGCTGTCTACCT
5461
[′CCTCTTCGTGCA
5720
[′CCTCTTCGTGCA


(TRPM6):c.3173A>G



CTTCGTGCAATRTAT

ATRTATCATCA′]

ATRTATCATCA′]


(p.Tyr1058Cys)



CATCATGGTGAACC










TGTTGATT′]






NM_006642.3
10806
SDCCAG8
5259
[′AATAAACCCTCTG
5462
[′CCTCTGCTTTTGC
5721
[′CCTCTGCTTTTGC


(SDCCAG8):c.2212A>G



CTTTTGCTCTATRGT

TCTATRGTTA′]

TCTATRGTTA′]






TAATCAGCTCAAAG










ATTTGTTGC′]






NM_003560.2
8398
PLA2G6
5260
[′CAGCATGCCCTGCT
5463
[′CCCTGCTCTGTG
5722-
[′CCCTGCTCTGTG


(PLA2G6):c.1349-2A>G



CTGTGCCTCACRGA

CCTCACRGAAC′]
5723
CCTCACRGAAC′,






ACTACAGGATCTCA



′CCTGCTCTGTGCC






TGCACATCT′]



TCACRGAACT′]









Example 6: Next Generation C to T Editors

Other families of cytidine deaminases as alternatives to base editor 3 (BE3) constructs were examined. The different C to T editors were developed to have a narrow or different editing window, alternate sequence specificity to expand targetable substrates, and to have higher activity.


Using the methods described in Example 4, the pmCDA1 (cytidine deaminase 1 from Petromyzon marinus) activity at the HeK-3 site is evaluated (FIG. 42). The pmCDA1-nCas9-UGI-NLS (nCas9 indicates the Cas9 nickase described herein) construct is active on some sites (e.g., the C bases on the complementary strand at position 9, 5, 4, and 3) that are not accessible with rAPOBEC1 (BE3).


The pmCDA1 activity at the HeK-2 site is given in FIG. 43. The pmCDA1-XTEN-nCas9-UGI-NLS construct is active on sites adjacent to “G,” while rAPOBEC1 analog (BE3 construct) has low activity on “C”s that are adjacent to “G”s, e.g., the C base at position 11 on the complementary strand.


The percent of total sequencing reads with target C converted to T (FIG. 44), C converted to A (FIG. 45), and C converted to G (FIG. 46) are shown for CDA and APOBEC1 (the BE3 construct).


The huAPOBEC3G activity at the HeK-2 site is shown in FIG. 47. Two constructs were used: huAPOBEC3G-XTEN-nCas9-UGI-NLS and huAPOBEC3G*(D316R_D317R)-XTEN-nCas9-UGI-NLS. The huAPOBEC3G-XTEN-nCas9-UGI-NLS construct has different sequence specificity than rAPOBEC1 (BE3), as shown in FIG. 47, the editing window appears narrow, as indicated by APOBEC3G's decreased activity at position 4 compared to APOBEC1. Mutations made in huAPOBEC3G (D316R and D317R) increased ssDNA binding and resulted in an observable effect on expanding the sites which were edited (compare APOBEC3G with APOBEC3G_RR in FIG. 47). Mutations were chosen based on APOBEC3G crystal structure, see: Holden et al., Crystal structure of the anti-viral APOBEC3G catalytic domain and functional implication. Nature. (2008); 121-4, the entire contents of which are incorporated herein by reference.


Example 7: pmCDA1/huAPOBEC3G/rAPOBEC1 Work in E. coli

LacZ selection optimization for the A to I conversion was performed using a bacterial strain with lacZ encoded on the F plasmid. A critical glutamic acid residue was mutated (e.g., GAG to GGG, Glu to Gly mutation) so that G to A by a cytidine deaminase would restore lacZ activity (FIG. 48). Strain CC102 was selected for the selection assay. APOBEC1 and CDA constructs were used in a selection assay to optimize G to A conversion.


To evaluate the the effect of copy number of the plasmids encoding the deaminase constructs on lacZ reversion frequency, the CDA and APOBEC1 deaminases were cloned into 4 plasmids with different replication origins (hence different copy numbers), SC101, CloDF3, RSF1030, and PUC (copy number: PUC>RSF1030>CloDF3>SC101) and placed under an inducible promoter. The plasmids were individually transformed into E. coli cells harboring F plasmid containing the mutated LacZ gene. The expression of the deaminases were induced and LacZ activity was detected for each construct (FIG. 49). As shown in FIG. 49, CDA exhibited significantly higher activity than APOBEC1 in all instances, regardless of the plasmid copy number the deaminases were cloned in. Further, In terms of the copy number, the deaminase activity was positively correlated with the copy number of the plasmid they are cloned in, i.e., PUC>CloDF3>SC101.


LacZ reversions were confirmed by sequencing of the genomic DNA at the lacZ locus. To obtain the genomic DNA containing the corrected LacZ gene, cells were grown media containing X-gal, where cells having LacZ activity form blue colonies. Blue colonies were selected and grown in minimal media containing lactose. The cells were spun down, washed, and re-plated on minimal media plates (lactose). The blue colony at the highest dilution was then selected, and its genomic DNA was sequenced at the lacZ locus (FIG. 50).


A chloramphenicol reversion assay was designed to test the activity of different cytidine deaminases (e.g., CDA, and APOBEC1). A plasmid harboring a mutant CAT1 gene which confers chloramphenicol resistance to bacteria is constructed with RSF1030 as the replication origin. The mutant CAT1 gene encodings a CAT1 protein that has a H195R (CAC to CGC) mutation, rendering the protein inactive (FIG. 51). Deamination of the C base-paired to the G base in the CGC codon would convert the codon back to a CAC codon, restoring the activity of the protein. As shown in FIG. 52, CDA outperforms rAPOBEC in E. coli in restoring the activity of the chloramphenicol resistance gene. The minimum inhibitory concentration (MIC) of chlor in S1030 with the selection plasmid (pNMG_ch_5) was approximately 1 μg/mL. Both rAPOBEC-XTEN-dCas9-UGI and CDA-XTEN-dCas9-UGI induced DNA correction on the selection plasmid (FIG. 53).


Next, the huAPOBEC3G-XTEN-dCas9-UGI protein was tested in the same assay. Interestingly, huAPOBEC3G-XTEN-dCas9-UGI exhibited different sequence specificity than the rAPOBEC1-XTEN-dCas9-UGI fusion protein. Only position 8 was edited with APOBEC3G-XTEN-dCas9-UGI fusion, as compared to the rAPOBEC11-XTEN-dCas9-UGIfusion (in which positions 3, 6, and 8 were edited) (FIG. 54).


Example 8: C to T Base Editors with Less Off Target Editing

Current base editing technologies allow for the sequence-specific conversion of a C:G base pair into a T:A base pair in genomic DNA. This is done via the direct catalytic conversion of cytosine to uracil by a cytidine deaminase enzyme and thus, unlike traditional genome editing technologies, does not introduce double-stranded DNA breaks (DSBs) into the DNA as a first step. See, Komor, A. C., Kim, Y. B., Packer, M. S., Zuris, J. A., and Liu, D. R. (2016), “Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage.” Nature 533, 420-424; the entire contents of which are incorporated by reference herein. Instead, catalytically dead SpCas9 (dCas9) or a SpCas9 nickase (dCas9(A840H)) is tethered to a cytidine deaminase enzyme such as rAPOBEC1, pmCDA1, or hAPOBEC3G. The genomic locus of interest is encoded by an sgRNA, and DNA binding and local denaturation is facilitated by the dCas9 portion of the fusion. However, just as wt dCas9 and wt Cas9 exhibit off-target DNA binding and cleavage, current base editors also exhibit C to T editing at Cas9 off-target loci, which limits their therapeutic usefulness.


It has been reported that the introduction of just three to four mutations into SpCas9 that neutralize nonspecific electrostatic interactions between the protein and the sugar-phosphate backbone of its target DNA, increases the DNA binding specificity of SpCas9. See, Kleinstiver, B. P., Pattanayak, V., Prew, M. S., Tsai, S. Q., Nguyen, N. T., Zheng, Z., and Joung, J. K. (2016) “High-fidelity CRISPR-Cas9 nucleases with no detectable genome-wide off-target effects.” Nature 529, 490-495; and Slaymaker, I. M., Gao, L., Zetsche, B., Scott, D. A., Yan, W. X., and Zhang, F. (2015) “Rationally engineered Cas9 nucleases with improved specificity. Science 351, 84-88; the entire contents of each are hereby incorporated by reference herein. Four reported neutralizing mutations were therefore incorporated into the initially reported base editor BE3 (SEQ ID NO: 285), and found that off-target C to T editing of this enzyme is also drastically reduced (FIG. 55), with no decrease in on-target editing (FIG. 56).


As shown in FIG. 55, HEK293T cells were transfected with plasmids expressing BE3 or HF-BE3 and a sgRNA matching the EMX1 sequence using Lipofectamine 2000. Three days after transfection, genomic DNA was extracted, amplified by PCR, and analyzed by high-throughput DNA sequencing at the on-target locus, plus the top ten known Cas9 off-target loci for the EMX1 sgRNA, as previously determined by Joung and coworkers using the GUIDE-seq method. See Tsai, S. Q., Zheng, Z., Nguyen, N. T., Liebers, M., Topkar, V. V., Thapar, V., Wyvekens, N., Khayter, C., Iafrate, A. J., Le, L. P., et al. (2015) “GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases.” Nat Biotech 33, 187-197; the entire contents of which are incorporated by reference herein. EMX1 off-target 5 locus did not amplify and is not shown. Sequences of the on-target and off-target protospacers and protospacer adjacent motifs (PAMs) are displayed (FIG. 55). Cellular C to T conversion percentages, defined as the percentage of total DNA sequencing reads with T at each position of an original C within the protospacer, are shown for BE3 and HF-BE3.


In FIG. 56, HEK293T cells were transfected with plasmids expressing BE3 or HF-BE3 and sgRNAs matching the genomic loci indicated using Lipofectamine 2000. Three days after transfection, genomic DNA was extracted, amplified by PCR, and analyzed by high-throughput DNA sequencing at the on-target loci. The percentage of total DNA sequencing reads with all four bases at the target Cs within each protospacer are shown for treatment with BE3 or HF-BE3 (FIG. 56). Frequencies of indel formation are shown as well.









Primary Protein Sequence 


of HF-BE3 (SEQ ID NO: 285):


MSSETGPVAVDPTLRRRIEPHEFEVFFDPRELRKETCLLYEINWGGRHSI





WRHTSQNTNKHVEVNFIEKFTTERYFCPNTRCSITWFLSWSPCGECSRAI





TEFLSRYPHVTLFIYIARLYHHADPRNRQGLRDLISSGVTIQIMTEQESG





YCWRNFVNYSPSNEAHWPRYPHLWVRLYVLELYCIILGLPPCLNILRRKQ





PQLTFFTIALQSCHYQRLPPHILWATGLKSGSETPGTSESATPESDKKYS





IGLAIGTNSVGWAVITDEYKVPSKKFKVLGNTDRHSIKKNLIGALLFDSG





ETAEATRLKRTARRRYTRRKNRICYLQEIFSNEMAKVDDSFFHRLEESFL





VEEDKKHERHPIFGNIVDEVAYHEKYPTIYHLRKKLVDSTDKADLRLIYL





ALAHMIKFRGHFLIEGDLNPDNSDVDKLFIQLVQTYNQLFEENPINASGV





DAKAILSARLSKSRRLENLIAQLPGEKKNGLFGNLIALSLGLTPNFKSNF





DLAEDAKLQLSKDTYDDDLDNLLAQIGDQYADLFLAAKNLSDAILLSDIL





RVNTEITKAPLSASMIKRYDEHHQDLTLLKALVRQQLPEKYKEIFFDQSK





NGYAGYIDGGASQEEFYKFIKPILEKMDGTEELLVKLNREDLLRKQRTFD





NGSIPHQIHLGELHAILRRQEDFYPFLKDNREKIEKILTFRIPYYVGPLA





RGNSRFAWMTRKSEETITPWNFEEVVDKGASAQSFIERMTAFDKNLPNEK





VLPKHSLLYEYFTVYNELTKVKYVTEGMRKPAFLSGEQKKAIVDLLFKTN





RKVTVKQLKEDYFKKIECFDSVEISGVEDRFNASLGTYHDLLKIIKDKDF





LDNEENEDILEDIVLTLTLFEDREMIEERLKTYAHLFDDKVMKQLKRRRY





TGWGALSRKLINGIRDKQSGKTILDFLKSDGFANRNFMALIHDDSLTFKE





DIQKAQVSGQGDSLHEHIANLAGSPAIKKGILQTVKVVDELVKVMGRHKP





ENIVIEMARENQTTQKGQKNSRERMKRIEEGIKELGSQILKEHPVENTQL





QNEKLYLYYLQNGRDMYVDQELDINRLSDYDVDHIVPQSFLKDDSIDNKV





LTRSDKNRGKSDNVPSEEVVKKMKNYWRQLLNAKLITQRKFDNLTKAERG





GLSELDKAGFIKRQLVETRAITKHVAQILDSRMNTKYDENDKLIREVKVI





TLKSKLVSDFRKDFQFYKVREINNYHHAHDAYLNAVVGTALIKKYPKLES





EFVYGDYKVYDVRKMIAKSEQEIGKATAKYFFYSNIMNFFKTEITLANGE





IRKRPLIETNGETGEIVWDKGRDFATVRKVLSMPQVNIVKKTEVQTGGFS





KESILPKRNSDKLIARKKDWDPKKYGGFDSPTVAYSVLVVAKVEKGKSKK





LKSVKELLGITIMERSSFEKNPIDFLEAKGYKEVKKDLIIKLPKYSLFEL





ENGRKRMLASAGELQKGNELALPSKYVNFLYLASHYEKLKGSPEDNEQKQ





LFVEQHKHYLDEIIEQISEFSKRVILADANLDKVLSAYNKHRDKPIREQA





ENIIHLFTLTNLGAPAAFKYFDTTIDRKRYTSTKEVLDATLIHQSITGLY





ETRIDLSQLGGDSGGSTNLSDIIEKETGKQLVIQESILMLPEEVEEVIGN





KPESDILVHTAYDESTDENVMLLTSDAPEYKPWALVIQDSNGENKIKMLS





GGSPKKKRKV






Example 9: Development of Base Editors that Use Cas9 Variants and Modulation of the Base Editor Processivity to Increase the Target Range and Precision of the Base Editing Technology

Unlike traditional genome editing platforms, base editing technology allows precise single nucleotide changes in the DNA without inducing double-stranded breaks (DSBs). See, Komor, A. C. et al. Nature 533, 420-424 (2016). The current generation of base editor uses the NGG PAM exclusively. This limits its ability to edit desired bases within the genome, as the base editor needs to be placed at a precise location where the target base is placed within a 4-base region (the ‘deamination window’), approximately 15 bases upstream of the PAM. See, Komor, A. C. et al. Nature 533, 420-424 (2016). Moreover, due to the high processivity of cytidine deaminase, the base editor may convert all cytidines within its deamination window into thymidines, which could induce amino acid changes other than the one desired by the researcher. See, Komor, A. C. et al. Nature 533, 420-424 (2016).


Expanding the Scope of Base Editing Through the Development of Base Editors with Cas9 Variants


Cas9 homologs and other RNA-guided DNA binders that have different PAM specificities were incorporated into the base editor architecture. See, Kleinstiver, B. P. et al. Nature 523, 481-485 (2015); Kleinstiver, B. P. et al. Nature Biotechnology 33, 1293-1298 (2015); and Zetsche, B. et al. Cell 163, 759-771 (2015); the entire contents of each are incorporated by reference herein. Furthermore, innovations that have broadened the PAM specificities of various Cas9 proteins were also incorporated to expand the target reach of the base editor even more. See, Kleinstiver, B. P. et al. Nature 523, 481-485 (2015); and Kleinstiver, B. P. et al. Nature Biotechnology 33, 1293-1298 (2015). The current palette of base editors is summarized in Table 4.









TABLE 4







New base editors made from Cas9 Variants












Base Editor
Reference for


Species
PAM
Name
Cas9 variant






S. pyogenes

...NGG
BE3
Wild-type



...NGA
VQR BE3 or
Kleinstiver, B. P.




EQR BE3
et al.



...NGCG
VRER BE3
Kleinstiver, B. P.





et al.



S. aureus

...NNGRRT
SaBE3
Wild-type



...NNNRRT
SaKKH BE3
Kleinstiver, B. P.





et al.



L. bacterium

TTTN...
dCpf1 BE2
Zetsche, B. et al.










Modulating Base Editor's Processivity Through Site-Directed Mutagenesis of rAPOBEC1


It was reasoned that the processivity of the base editor could be modulated by making point mutations in the deaminase enzyme. The incorporation of mutations that slightly reduce the catalytic activity of deaminase in which the base editor could still catalyze on average one round of cytidine deamination but was unlikely to access and catalyze another deamination within the relevant timescale were pursued. In effect, the resulting base editor would have a narrower deamination window.


rAPOBEC1 mutations probed in this work are listed in Table 5. Some of the mutations resulted in slight apparent impairment of rAPOBEC1 catalysis, which manifested as preferential editing of one cytidine over another when multiple cytidines are found within the deamination window. Combining some of these mutations had an additive effect, allowing the base editor to discriminate substrate cytidines with higher stringency. Some of the double mutants and the triple mutant allowed selective editing of one cytidine among multiple cytidines that are right next to one another (FIG. 57).









TABLE 5







rAPOBEC1 Point Mutations Investigated









rAPOBEC1 mutation
Corresponding mutation



studied in this work
in APOBEC3G
Reference





H121R/H122R
D315R/D316R
Holden, L. G. et al.


R126A
R320A
Chen, K-M. et al.


R126E
R320E
Chen, K-M. et al.


R118A
R313A
Chen, K-M. et al.


W90A
W285A
Chen, K-M. et al.


W90Y
W285Y



R312E
R326E










Base Editor PAM Expansion and Processivity Modulation


The next generation of base editors were designed to expand editable cytidines in the genome by using other RNA-guided DNA binders (FIG. 58). Using a NGG PAM only allows for a single target within the “window” whereas the use of multiple different PAMs allows for Cas9 to be positioned anywhere to effect selective deamination. A variety of new base editors have been created from Cas9 variants (FIG. 59 and Table 4). Different PAM sites (NGA, FIG. 60; NGCG, FIG. 61; NNGRRT, FIG. 62; and NNHRRT, FIG. 63) were explored. Selective deamination was successfully achieved through kinetic modulation of cytidine deaminase point mutagenesis (FIG. 65 and Table 5).


The effect of various mutations on the deamination window was then investigated in cell culture using spacers with multiple cytidines (FIGS. 66 and 67).


Further, the effect of various mutations on different genomic sites with limited numbers of cytidines was examined (FIGS. 68 to 71). It was found that approximately one cytidine will be edited within the deamination window in the spacer, while the rest of the cytidines will be left intact. Overall, the preference for editing is as follows: C6>C5>>C7≈C4.


Base Editing Using Cpf1


Cpf1, a Cas9 homolog, can be obtained as AsCpf1, LbCpf1, or from any other species. Schematics of fusion constructs, including BE2 and BE3 equivalents, are shown in FIG. 73. The BE2 equivalent uses catalytically inactive Cpf2 enzyme (dCpf1) instead of Cas9, while the BE3 equivalent includes the Cpf1 mutant, which nicks the target strand. The bottom schematic depicts different fusion architectures to combine the two innovations illustrated above it (FIG. 73). The base editing results of HEK293T cell TTTN PAM sites using Cpf1 BE2 were examined with different spacers (FIGS. 64A to 64C). In some embodiments, Cpf1 may be used in place of a Cas9 domain in any of the base editors provided herein. In some embodiments, the Cpf1 is a protein that is at lesst 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99%, or 99.5% identical to SEQ ID NO 313.









Full Protein Sequence of Cpf1 (SEQ ID NO: 313):


MSIYQEFVNKYSLSKTLRFELIPQGKTLENIKARGLILDDEKRAKDYKKA





KQIIDKYHQFFIEEILSSVCISEDLLQNYSDVYFKLKKSDDDNLQKDFKS





AKDTIKKQISEYIKDSEKFKNLFNQNLIDAKKGQESDLILWLKQSKDNGI





ELFKANSDITDIDEALEIIKSFKGWTTYFKGFHENRKNVYSSNDIPTSII





YRIVDDNLPKFLENKAKYESLKDKAPEAINYEQIKKDLAEELTFDIDYKT





SEVNQRVFSLDEVFEIANFNNYLNQSGITKFNTIIGGKFVNGENTKRKGI





NEYINLYSQQINDKTLKKYKMSVLFKQILSDTESKSFVIDKLEDDSDVVT





TMQSFYEQIAAFKTVEEKSIKETLSLLFDDLKAQKLDLSKIYFKNDKSLT





DLSQQVFDDYSVIGTAVLEYITQQIAPKNLDNPSKKEQELIAKKTEKAKY





LSLETIKLALEEFNKHRDIDKQCRFEEILANFAAIPMIFDEIAQNKDNLA





QISIKYQNQGKKDLLQASAEDDVKAIKDLLDQTNNLLHKLKIFHISQSED





KANILDKDEHFYLVFEECYFELANIVPLYNKIRNYITQKPYSDEKFKLNF





ENSTLANGWDKNKEPDNTAILFIKDDKYYLGVMNKKNNKIFDDKAIKENK





GEGYKKIVYKLLPGANKMLPKVFFSAKSIKFYNPSEDILRIRNHSTHTKN





GSPQKGYEKFEFNIEDCRKFIDFYKQSISKHPEWKDFGFRFSDTQRYNSI





DEFYREVENQGYKLTFENISESYIDSVVNQGKLYLFQIYNKDFSAYSKGR





PNLHTLYWKALFDERNLQDVVYKLNGEAELFYRKQSIPKKITHPAKEAIA





NKNKDNPKKESVFEYDLIKDKRFTEDKFFFHCPITINFKSSGANKFNDEI





NLLLKEKANDVHILSIDRGERHLAYYTLVDGKGNIIKQDTFNIIGNDRMK





TNYHDKLAAIEKDRDSARKDWKKINNIKEMKEGYLSQVVHEIAKLVIEYN





AIVVFEDLNFGFKRGRFKVEKQVYQKLEKMLIEKLNYLVFKDNEFDKTGG





VLRAYQLTAPFETFKKMGKQTGIIYYVPAGFTSKICPVTGFVNQLYPKYE





SVSKSQEFFSKFDKICYNLDKGYFEFSFDYKNFGDKAAKGKWTIASFGSR





LINFRNSDKNHNWDTREVYPTKELEKLLKDYSIEYGHGECIKAAICGESD





KKFFAKLTSVLNTILQMRNSKTGTELDYLISPVADVNGNFFDSRQAPKNM





PQDADANGAYHIGLKGLMLLGRIKNNQEGKKLNLVIKNEEYFEFVQNRNN






Example 10: Increased Fidelity of Base Editing

Examining the difference between plasmid delivery of BE3 and HF-BE3, it was found that the two edit on-target loci with comparable efficiency (FIGS. 74 and 75). However, HF-BE3 edited off-target loci much less than BE3, meaning that HF-BE3 has a much higher DNA specificity than BE3 (FIG. 76). Deaminase protein lipofection to HEK cells demonstrated that protein delivery of BE3 results in comparable on-target activity, but much better specificity, than plasmid DNA delivery of BE3. Using improved transfection procedures and better plasmids (n=2), the experiment used the following conditions: protein delivery was 125 nM Cas9:sgRNA complex, plasmid delivery was 750ng BE3/HF-BE3 plasmid+250ng sgRNA plasmid, and lipofection was with 1.5 μL of Lipofectamine 2000 per well. EMX-1 off target site 2 and FANCF off-target site 1 showed the most off-target editing with BE3, compared to all of the off-targets assayed (FIGS. 77 and 78), while HEK-3 showed no significant editing at off-targets for any of the delivery methods (FIG. 79). HEK-4 shows some C-to-G editing on at the on-target site, while its off-target sites 1, 3, and 4 showed the most off-target editing of all the assayed sites (FIG. 80).


Delivery of BE3 Protein Via Micro-Injection to Zebrafish


TYR guide RNAs were tested in an in vitro assay for sgRNA activity (FIGS. 81 and 82). The % HTS reads shows how many C residues were converted to T residues during a 2h incubation with purified BE3 protein and PCR of the resulting product. Experiments used an 80-mer synthetic DNA substrate with the target deamination site in 60 bp of its genomic context. This is not the same as % edited DNA strands because only one strand was nicked, so the product is not amplified by PCR. The proportion of HTS reads edited is equal to x/(2−x), where x is the actual proportion of THS reads edited. For 60% editing, the actual proportion of bases edited is 75%. “Off target” is represents BE3 incubated with the same DNA substrate, while bound to an off-target sgRNA. It was found sgRNAs sgRH_13, sgHR_17, and possibly sgHR_16 appeared to be promising targets for in vivo injection experiments.


The delivery of BE3 protein in was tested in vivo in zebrafish. Zebrafish embryos (n=16-24) were injected with either scrambled sgRNA, sgHR_13, sgHR_16, or sgHR_17 and purified BE3. Three embryos from each condition were analyzed independently (single embryo) and for each condition, all of the injected embryos were pooled and sequenced as a pool. The results are shown in FIGS. 83 to 85.


Example 11: Uses of Base Editors to Treat Disease

Base editors or complexes provided herein (e.g., BE3) may be used to modify nucleic acids. For example, base editors may be used to change a cytosine to a thymine in a nucleic acid (e.g., DNA). Such changes may be made to, inter alia, alter the amino acid sequence of a protein, to destroy or create a start codon, to create a stop codon, to disrupt splicing donors, to disrupt splicing acceptors or edit regulatory sequences. Examples of possible nucleotide changes are shown in FIG. 86.


Base editors or complexes provided herein (e.g., BE3) may be used to edit an isoform of Apolipoprotein E in a subject. For example, an Apolipoprotein E isoform may be edited to yield an isoform associated with a lower risk of developing Alzheimer's disease. Apolipoprotein E has four isoforms that differ at amino acids 112 and 158. APOE4 is the largest and most common genetic risk factor for late-onset Alzheimer's disease. Arginine residue 158 of APOE4, encoded by the nucleic acid sequence CGC, may be changed to a cysteine by using a base editor (e.g., BE3) to change the CGC nucleic acid sequence to TGC, which encodes cysteine at residue 158. This change yields an APOE3r isoform, which is associated with lower Alzheimer's disease risk. See FIG. 87.


It was tested whether base editor BE3 could be used to edit APOE4 to APOE3r in mouse astrocytes (FIG. 88). APOE 4 mouse astrocytes were nucleofected with Cas9+ template or BE3, targeting the nucleic acid encoding Arginine 158 of APOE4. The Cas9+ template yielded only 0.3% editing with 26% indels, while BE3 yielded 75% editing with 5% indels. Two additional base-edited cytosines are silent and do not yield changes to the amino acid sequence (FIG. 88).


Base editors or complexes provided herein may be used to treat prion protein diseases such as Creutzfeldt-Jakob disease and fatal familial insomnia, for example, by introducing mutations into a PRNP gene. Reverting PRNP mutations may not yield therapeutic results, and intels in PRNP may be pathogenic. Accordingly, it was tested whether PRNP could be mutated using base editors (e.g., BE3) to introduce a premature stop codon in the PRNP gene. BE3, associated with its guide RNA, was introduced into HEK cells or glioblastoma cells and was capable of editing the PRNP gene to change the encoded arginine at residue 37 to a stop codon. BE3 yielded 41% editing (FIG. 89).


Additional genes that may be edited include the following: APOE editing of Arg 112 and Arg 158 to treat increased Alzheimer's risk; APP editing of Ala 673 to decrease Alzheimer's risk; PRNP editing of Arg 37 to treat fatal familial insomnia and other prion protein diseases; DMD editing of the exons 23 and 51 splice sites to treat Duchenne muscular dystrophy; FTO editing of intron 1 to treat obesity risk; PDS editing of exon 8 to treat Pendred syndrome (genetic deafness); TMC1 editing of exon 8 to treat congenital hearing loss; CYBB editing of various patient-relevant mutations to treat chronic granulomatous disease. Additional diseases that may be treated using the base editors provided herein are shown in Table 6, below.


UGI also plays a key role. Knocking out UDG (which UGI inhibits) was shown to dramatically improve the cleanliness and efficiency of C to T base editing (FIG. 90). Furthermore, base editors with nickase and without UGI were shown to produce a mixture of outcomes, with very high indel rates (FIG. 91).


Example 12: Expanding the Targeting Scope of Base Editing

Base editing is a new approach to genome editing that uses a fusion protein containing a catalytically defective Streptococcus pyogenes Cas9, a cytidine deaminase, and an inhibitor of base excision repair to induce programmable, single-nucleotide C→T (or G→A) changes in DNA without generating double-strand DNA breaks, without requiring a donor DNA template, and without inducing an excess of stochastic insertions and deletions. The development of five new C→T (or G→A) base editors that use natural and engineered Cas9 variants with different protospacer-adjacent motif (PAM) specificities to expand the number of sites that can be targeted by base editing by 2.5-fold are described herein. Additionally, new base editors containing mutated cytidine deaminase domains that narrow the width of the apparent editing window from approximately 5 nucleotides to 1 or 2 nucleotides were engineered, enabling the discrimination of neighboring C nucleotides that would previously be edited with comparable efficiency. Together, these developments substantially increase the targeting scope of base editing.


CRISPR-Cas9 nucleases have been widely used to mediate targeted genome editing2. In most genome editing applications, Cas9 forms a complex with a single guide RNA (sgRNA) and induces a double-stranded DNA break (DSB) at the target site specified by the sgRNA sequence. Cells primarily respond to this DSB through the non-homologuous end-joining (NHEJ) repair pathway, which results in stochastic insertions or deletions (indels) that can cause frameshift mutations that disrupt the gene. In the presence of a donor DNA template with a high degree of homology to the sequences flanking the DSB, gene correction can be achieved through an alternative pathway known as homology directed repair (HDR).34 Unfortunately, under most non-perturbative conditions HDR is inefficient, dependent on cell state and cell type, and dominated by a larger frequency of indels.3,4 As most of the known genetic variations associated with human disease are point mutations5, methods that can more efficiently and cleanly make precise point mutations are needed.


Base editing, which enables targeted replacement of a C:G base pair with a T:A base pair in a programmable manner without inducing DSBs1, has been recently described. Base editing uses a fusion protein between a catalytically inactivated (dCas9) or nickase form of Streptococcus pyogenes Cas9 (SpCas9), a cytidine deaminase such as APOBEC1, and an inhibitor of base excision repair such as uracil glycosylase inhibitor (UGI) to convert cytidines into uridines within a five-nucleotide window specified by the sgRNA.1 The third-generation base editor, BE3, converts C:G base pairs to T:A base pairs, including disease-relevant point mutations, in a variety of cell lines with higher efficiency and lower indel frequency than what can be achieved using other genome editing methods1. Subsequent studies have validated the deaminase-dCas9 fusion approach in a variety of settings6,7.


Efficient editing by BE3 requires the presence of an NGG PAM that places the target C within a five-nucleotide window near the PAM-distal end of the protospacer (positions 4-8, counting the PAM as positions 21-23)1. This PAM requirement substantially limits the number of sites in the human genome that can be efficiently targeted by BE3, as many sites of interest lack an NGG 13- to 17-nucleotides downstream of the target C. Moreover, the high activity and processivity of BE3 results in conversion of all Cs within the editing window to Ts, which can potentially introduce undesired changes to the target locus. Herein, new C:G to T:A base editors that address both of these limitations are described.


It was thought that any Cas9 homolog that binds DNA and forms an “R-loop” complex8 containing a single-stranded DNA bubble could in principle be converted into a base editor. These new base editors would expand the number of targetable loci by allowing non-NGG PAM sites to be edited. The Cas9 homolog from Staphylococcus aureus (SaCas9) is considerably smaller than SpCas9 (1053 vs. 1368 residues), can mediate efficient genome editing in mammalian cells, and requires an NNGRRT PAM9. SpCas9 was replaced with SaCas9 in BE3 to generate SaBE3 and transfected HEK293T cells with plasmids encoding SaBE3 and sgRNAs targeting six human genomic loci (FIGS. 92A and 92B). After 3 d, the genomic loci were subjected to high-throughput DNA sequencing (HTS) to quantify base editing efficiency. SaBE3 enabled C to T base editing of target Cs at a variety of genomic sites in human cells, with very high conversion efficiencies (approximately 50-75% of total DNA sequences converted from C to T, without enrichment for transfected cells) arising from targeting Cs at positions 6-11. The efficiency of SaBE3 on NNGRRT-containing target sites in general exceeded that of BE3 on NGG-containing target sites1. Perhaps due to its higher average efficiency, SaBE3 can also result in detectable base editing at target Cs at positions outside of the canonical BE3 activity window (FIG. 92C). In comparison, BE3 showed significantly reduced editing under the same conditions (0-11%), in accordance with the known SpCas9 PAM preference (FIG. 106A)10. These data show that SaBE3 can facilitate very efficient base editing at sites not accessible to BE3.


The targeting range of base editors was further expanded by applying recently engineered Cas9 variants that expand or alter PAM specificities. Joung and coworkers recently reported three SpCas9 mutants that accept NGA (VQR-Cas9), NGAG (EQR-Cas9), or NGCG(VRER-Cas9) PAM sequences11. In addition, Joung and coworkers engineered a SaCas9 variant containing three mutations (SaKKH-Cas9) that relax its PAM requirement to NNNRRT12. The SpCas9 portion of BE3 was replaced with these four Cas9 variants to produce VQR-BE3, EQR-BE3, VRER-BE3, and SaKKH-BE3, which target NNNRRT, NGA, NGAG, and NGCG PAMs respectively. HEK293T cells were transfected with plasmids encoding these constructs and sgRNAs targeting six genomic loci for each new base editor, and measured C to T base conversions using HTS.


SaKKH-BE3 edited sites with NNNRRT PAMs with efficiencies up to 62% of treated, non-enriched cells (FIG. 92D). As expected, SaBE3 was unable to efficiently edit targets containing PAMs that were NNNHRRT (where H=A, C, or T) (FIG. 92D). VQR-BE3, EQR-BE3, and VRER-BE3 exhibited more modest, but still substantial base editing efficiencies of up to 50% of treated, non-enriched cells at genomic loci with the expected PAM requirements with an editing window similar to that of BE3 (FIGS. 92E and 92F). Base editing efficiencies of VQR-BE3, EQR-BE3, and VRER-BE3 in general closely paralleled the reported PAM requirements of the corresponding Cas9 nucleases; for example, EQR-BE3 was unable to efficiently edit targets containing NGAH PAM sequences (FIG. 92F). In contrast, BE3 was unable to edit sites with NGA or NGCG PAMs efficiently (0-3%), likely due to its PAM restrictions (FIG. 106B).


Collectively, the properties of SaBE3, SaKKH-BE3, VQR-BE3, EQR-BE3, and VRER-BE3 establish that base editors exhibit a modularity that facilitates their ability to exploit Cas9 homologs and engineered variants.


Next, base editors with altered activity window widths were developed. All Cs within the activity window of BE3 can be efficiently converted to Ts1. The ability to modulate the width of this window would be useful in cases in which it is important to edit only a subset of Cs present in the BE3 activity window.


The length of the linker between APOBEC1 and dCas9 was previously observed to modulate the number of bases that are accessible by APOBEC1 in vitro1. In HEK293T cells, however, varying the linker length did not significantly modulate the width of the editing window, suggesting that in the complex cellular milieu, the relative orientation and flexibility of dCas9 and the cytidine deaminase are not strongly determined by linker length (FIG. 96). Next, it was thought that truncating the 5′ end of the sgRNA might narrow the base editing window by reducing the length of single-stranded DNA accessible to the deaminase upon formation of the RNA-DNA heteroduplex. HEK293T cells were co-transfected with plasmids encoding BE3 and sgRNAs of different spacer lengths targeting a locus with multiple Cs in the editing window. No consistent changes in the width of base editing when using truncated sgRNAs with 17- to 19-base spacers were observed (FIGS. 95A to 95B). Truncating the sgRNA spacer to fewer than 17 bases resulted in large losses in activity (FIG. 95A).


As an alternative approach, it was thought that mutations to the deaminase domain might narrow the width of the editing window through multiple possible mechanisms. First, some mutations may alter substrate binding, the conformation of bound DNA, or substrate accessibility to the active site in ways that reduce tolerance for non-optimal presentation of a C to the deaminase active site. Second, because the high activity of APOBEC1 likely contributes to the deamination of multiple Cs per DNA binding event,1, 13, 14 mutations that reduce the catalytic efficiency of the deaminase domain of a base editor might prevent it from catalyzing successive rounds of deamination before dissociating from the DNA. Once any C:G to T:A editing event has taken place, the sgRNA no longer perfectly matches the target DNA sequence and re-binding of the base editor to the target locus should be less favorable. Both strategies were tested in an effort to discover new base editors that distinguish among multiple cytidines within the original editing window.


Given the absence of an available APOBEC1 structure, several mutations previously reported to modulate the catalytic activity of APOBEC3G, a cytidine deaminase from the same family that shares 42% sequence similarity of its active site-containing domain to that of APOBEC1, were identified15. Corresponding APOBEC1 mutations were incorporated into BE3 and evaluated their effect on base editing efficiency and editing window width in HEK293T cells at two C-rich genomic sites containing Cs at positions 3, 4, 5, 6, 8, 9, 10, 12, 13, and 14 (site A); or containing Cs at positions 5, 6, 7, 8, 9, 10, 11, and 13 (site B).


The APOBEC1 mutations R118A and W90A each led to dramatic loss of base editing efficiency (FIG. 97C). R132E led to a general decrease in editing efficiency but did not change the substantially narrow the shape of the editing window (FIG. 97C). In contrast, several mutations that narrowed the width of the editing window while maintaining substantial editing efficiency were found (FIGS. 93A and 97C). The “editing window width” was defined to represent the artificially calculated window width within which editing efficiency exceeds the half-maximal value for that target. The editing window width of BE3 for the two C-rich genomic sites tested was 5.0 (site A) and 6.1 (site B) nucleotides.


R126 in APOBEC1 is predicted to interact with the phosphate backbone of ssDNA13. Previous studies have shown that introducing the corresponding mutation into APOBEC3G decreased catalysis by at least 5-fold14. Interestingly, when introduced into APOBEC1 in BE3, R126A and R126E increased or maintained activity relative to BE3 at the most strongly edited positions (C5, C6, and C7), while decreasing editing activity at other positions (FIGS. 93A and 97C). Each of these two mutations therefore narrowed the width of the editing window at site A and site B to 4.4 and 3.4 nucleotides (R126A), or to 4.2 and 3.1 nucleotides (R126E), respectively (FIGS. 93A and 97C).


W90 in APOBEC1 (corresponding to W285 in APOBEC3G) is predicted to form a hydrophobic pocket in the APOBEC3G active site and assist in substrate binding13. Mutating this residue to Ala abrogated APOBEC3G's catalytic activity13. In BE3, W90A almost completely abrogated base editing efficiency (FIG. 97C). In contrast, it was found that W90Y only modestly decreased base editing activity while narrowing the editing window width at site A and site B to 3.8 and 4.9 nucleotides, respectively (FIG. 93A). These results demonstrate that mutations to the cytidine deaminase domain can narrow the activity window width of the corresponding base editors.


W90Y, R126E, and R132E, the three mutations that narrowed the editing window without drastically reducing base editing activity, were combined into doubly and triply mutated base editors. The double mutant W90Y+R126E resulted in a base editor (YE1-BE3) with BE3-like maximal editing efficiencies, but substantially narrowed editing window width (width at site A and site B=2.9 and 3.0 nucleotides, respectively (FIG. 93A). The W90Y+R132E base editor (YE2-BE3) exhibited modestly lower editing efficiencies (averaging 1.4-fold lower maximal editing yields across the five sites tested compared with BE3), and also substantially narrowed editing window width (width at site A and site B=2.7 and 2.8 nucleotides, respectively) (FIG. 97C). The R126E+R132E double mutant (EE-BE3) showed similar maximal editing efficiencies and editing window width as YE2-BE3 (FIG. 97C). The triple mutant W90Y+R126E+R132E (YEE-BE3) exhibited 2.0-fold lower average maximal editing yields but very little editing beyond the C6 position and an editing window width of 2.1 and 1.4 nucleotides for site A and site B, respectively (FIG. 97C). These data taken together indicate that mutations in the cytidine deaminase domain can strongly affect editing window widths, in some cases with minimal or only modest effects on editing efficiency.


The base editing outcomes of BE3, YE1-BE3, YE2-BE3, EE-BE3, and YEE-BE3 were further compared in HEK293T cells targeting four well-studied human genomic sites that contain multiple Cs within the BE3 activity window1. These target loci contained target Cs at positions 4 and 5 (HEK site 3), positions 4 and 6 (HEK site 2), positions 5 and 6 (EMX1), or positions 6, 7, 8, and 11 (FANCF). BE3 exhibited little (<1.2-fold) preference for editing any Cs within the position 4-8 activity window. In contrast, YE1-BE3, exhibited a 1.3-fold preference for editing C5 over C4 (HEK site 3), 2.6-fold preference for C6 over C4 (HEK site 2), 2.0-fold preference for C5 over C6 (EMX1), and 1.5-fold preference for C6 over C7 (FANCF) (FIG. 93B). YE2-BE3 and EE-BE3 exhibited somewhat greater positional specificity (narrower activity window) than YE1-BE3, averaging 2.4-fold preference for editing C5 over C4 (HEK site 3), 9.5-fold preference for C6 over C4 (HEK site 2), 2.9-fold preference for C5 over C6 (EMX1), and 2.6-fold preference for C7 over C6 (FANCF) (FIG. 93B). YEE-BE3 showed the greatest positional selectivity, with a 2.9-fold preference for editing C5 over C4 (HEK site 3), 29.7-fold preference for C6 over C4 (HEK site 2), 7.9-fold preference for C5 over C6 (EMX1), and 7.9-fold preference for C7 over C6 (FANCF) (FIG. 93B). The findings establish that mutant base editors can discriminate between adjacent Cs, even when both nucleotides are within the BE3 editing window.


The product distributions of these four mutants and BE3 were further analyzed by HTS to evaluate their apparent processivity. BE3 generated predominantly T4-T5 (HEK site 3), T4-T6 (HEK site 2), and T5-T6 (EMX1) products in treated HEK293T cells, resulting in, on average, 7.4-fold more products containing two Ts, than products containing a single T. In contrast, YE1-BE3, YE2-BE3, EE-BE3, and YEE-BE3 showed substantially higher preferences for singly edited C4-T5, C4-T6, and T5-C6 products (FIG. 93C). YE1-BE3 yielded products with an average single-T to double-T product ratio of 1.4. YE2-BE3 and EE-BE3 yielded products with an average single-T to double-T product ratio of 4.3 and 5.1, respectively (FIG. 93C). Consistent with the above results, the YEE-BE3 triple mutant favored single-T products by an average of 14.3-fold across the three genomic loci. (FIG. 93C). For the target site in which only one C is within the target window (HEK site 4, at position C5), all four mutants exhibited comparable editing efficiencies as BE3 (FIG. 98). These findings indicate that these BE3 mutants have decreased apparent processivity and can favor the conversion of only a single C at target sites containing multiple Cs within the BE3 editing window. These data also suggest a positional preference of C5>C6>C7≈C4 for these mutant base editors, although this preference could differ depending on the target sequence.


The window-modulating mutations in APOBEC1 were applied to VQR-BE3, allowing selective base editing of substrates at sites targeted by NGA PAM (FIG. 107A). However, when these mutations were applied to SaKKH-BE3, a linear decrease in base editing efficiency was observed without the improvement in substrate selectivity, suggesting a different kinetic equilibrium and substrate accessibility of this base editor than those of BE3 and its variants (FIG. 107B).


The five base editors with altered PAM specificities described in this study together increase the number of disease-associated mutations in the ClinVar database that can in principle be corrected by base editing by 2.5-fold (FIGS. 94A and 94B). Similarly, the development of base editors with narrowed editing windows approximately doubles the fraction of ClinVar entries with a properly positioned NGG PAM that can be corrected by base editing without comparable modification of a non-target C (from 31% for BE3 to 59% for YEE-BE3) (FIGS. 94A and 94B).


In summary, the targeting scope of base editing was substantially expanded by developing base editors that use Cas9 variants with different PAM specificities, and by developing a collection of deaminase mutants with varying editing window widths. In theory, base editing should be possible using other programmable DNA-binding proteins (such as Cpf116) that create a bubble of single-stranded DNA that can serve as a substrate for a single-strand-specific nucleotide deaminase enzyme.


Materials and Methods

Cloning. PCR was performed using Q5 Hot Start High-Fidelity DNA Polymerase (New England Biolabs). Plasmids for BE and sgRNA were constructed using USER cloning (New England Biolabs), obtained from previously reported plasmids1. DNA vector amplification was carried out using NEB 10 beta competent cells (New England Biolabs).


Cell culture. HEK293T (ATCC CRL-3216) were cultured in Dulbecco's Modified Eagle's Medium plus GlutaMax (ThermoFisher) supplemented with 10% (v/v) fetal bovine serum (FBS), at 37° C. with 5% CO2. Immortalized rat astrocytes containing the ApoE4 isoform of the APOE gene (Taconic Biosciences) were maintained in Dulbecco's Modified Eagle's Medium plus GlutaMax (ThermoFisher Scientific) supplemented with 10% (v/v) fetal bovine serum (FBS) and 200 μg/mL Geneticin (ThermoFisher Scientific).


Transfections. HEK293T cells were seeded on 48-well collagen-coated BioCoat plates (Corning) and transfected at approximately 85% confluency. 750 ng of BE and 250 ng of sgRNA expression plasmids were transfected using 1.5 μl of Lipofectamine 2000 (ThermoFisher Scientific) per well according to the manufacturer's protocol.


High-throughput DNA sequencing of genomic DNA samples. Transfected cells were harvested after 3 d and the genomic DNA was isolated using the Agencourt DNAdvance Genomic DNA Isolation Kit (Beckman Coulter) according to the manufacturer's instructions. Genomic regions of interest were amplified by PCR with flanking HTS primer pairs listed in the Supplementary Sequences. PCR amplification was carried out with Phusion hot-start II DNA polymerase (ThermoFisher) according to the manufacturer's instructions. PCR products were purified using RapidTips (Diffinity Genomics). Secondary PCR was performed to attach sequencing adaptors. The products were gel-purified and quantified using the KAPA Library Quantification Kit-Illumina (KAPA Biosystems). Samples were sequenced on an Illumina MiSeq as previously described1.


Data analysis. Nucleotide frequencies were assessed using a previously described MATLAB script1. Briefly, the reads were aligned to the reference sequence via the Smith-Waterman algorithm. Base calls with Q-scores below 30 were replaced with a placeholder nucleotide (N). This quality threshold results in nucleotide frequencies with an expected theoretical error rate of 1 in 1000.


Analyses of base editing processivity were performed using a custom python script. This program trims sequencing reads to the 20 nucleotide protospacer sequence as determined by a perfect match for the 7 nucleotide sequences that should flank the target site. These targets were then consolidated and sorted by abundance to assess the frequency of base editing products.


Bioinformatic analysis of the ClinVar database of human disease-associated mutations was performed in a manner similar to that previously described but with small adjustments1. These adjustments enable the identification of targets with PAMs of customizable length and sequence. In addition, this improved script includes a priority ranking of target C positions (C5>C6>C7>C8≈C4), thus enabling the identification of target sites in which the on-target C is either the only cytosine within the window or is placed at a position with higher predicted editing efficiency than any off-target C within the editing window.


REFERENCES FOR EXAMPLE 12



  • 1 Komor, A. C. et al. Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533, 420-424 (2016).

  • 2 Sander, J. D. & Joung, J. K. CRISPR-Cas systems for editing, regulating and targeting genomes. Nature biotechnology 32, 347-355 (2014).

  • 3 Cong, L. et al. Multiplex genome engineering using CRISPR/Cas systems. Science 339, 819-823 (2013).

  • 4 Ran, F. A. et al. Genome engineering using the CRISPR-Cas9 system. Nat. Protocols 8, 2281-2308 (2013).

  • 5 Landrum, M. J. et al. ClinVar: public archive of interpretations of clinically relevant variants. Nucleic Acids Res. 44, D862-D868 (2015).

  • 6 Nishida, K. et al. Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive immune systems. Science 353, aaf8729-1-8 (2016).

  • 7 Ma, Y. et al. Targeted AID-mediated mutagenesis (TAM) enables efficient genomic diversification in mammalian cells. Nat. Methods doi:10.1038/nmeth.4027 (2016).

  • 8 Jiang, F. et al. Structures of a CRISPR-Cas9 R-loop complex primed for DNA cleavage. Science 351, 867-71 (2016).

  • 9 Ran, F. A. et al. In vivo genome editing using Staphylococcus aureus Cas9. Nature 520, 186-191 (2015).

  • 10 Zhang, Y. et al. Comparison of non-canonical PAMs for CRISPR/Cas9-mediated DNA cleavage in human cells. Sci. Rep. 4, (2014).

  • 11 Kleinstiver, B. P. et. al. Engineered CRISPR-Cas9 nucleases with altered PAM specificities. Nature 523, 481-485 (2015).

  • 12 Kleinstiver, B. P. et. al. Broadening the targeting range of Staphylococcus aureus CRISPR-Cas9 by modifying PAM recognition. Nat. Biotechnol. 33, 1293-1298 (2015).

  • 13 Holden, L. G. et al. Crystal structure of the anti-viral APOBEC3G catalytic domain and functional implications. Nature 452, 121-124 (2008).

  • 14 Chen, K.-M. et al. Structure of the DNA deaminase domain of the HIV-1 restriction factor APOBEC3G. Nature 452, 116-119 (2008).

  • 15 Harris, R. S., Petersen-Mahrt, S. K. & Neuberger, M. S. RNA Editing Enzyme APOBEC1 and Some of Its Homologs Can Act as DNA Mutators. Molecular Cell 10, 1247-1253 (2002).

  • 16 Zetsche, B. et al. Cpf1 Is a Single RNA-Guided Endonuclease of a Class 2 CRISPR-Cas System. Cell 163, 759-771 (2015).



Example 13

Using improved transfection procedures and better plasmids, biological replicates (n=3) were used to install the four HF mutations into the Cas9 portion of BE3. The mutations do not significantly effect on-targeting editing with plasmid delivery (FIG. 99). At the tested concentration, BE3 protein delivery works; however, the on-target editing is lower than for plasmid delivery (FIG. 100). Protein delivery of BE3 with the HF mutations installed reduces on-targeting editing efficiency but still yields some edited cells (FIG. 101).


Both lipofection and installing HF mutations were shown to decrease off-target deamination events. For the four sites shown in FIG. 102, the off-target sitest (OT) with the highest GUIDE-Seq reads and deamination events were assayed (Komor et al., Nature, 2016). The specificity ratio was calculated by dividing the off-target editing by the on-target editing at the closest corresponding C. In cases where off-target editing was not detectable, the ratio was set to 100. Thus, a higher specificity ratio indicates a more specific construct. BE3 plasmid delivery showed much higher off-target/on-target editing than protein delivery of BE3, plasmid delivery of HF-BE3, or protein delivery of HF-BE3 (FIGS. 102 and 105).


Purified proteins HF-BE3 and BE3 were analyzed in vitro for their capabilities to convert C to T residues at different positions in the spacer with the most permissive motif. Both BE3 and HF-BE3 proteins were found to have the same “window” for base editing (FIGS. 103 and 104).


A list of the disease targets is given in Table 9. The base to be edited in Table 9 is indicated in bold and underlined.









TABLE 9







Base Editor Disease Targets













GENE
DISEASE
SPACER
PAM
EDITOR
DEFECT
CELL





RB1
RETINOBLASTOMA
AATCTAGTAAA
AAAAGT
SAKKH-BE3
SPLICING
J82




TAAATTGATGT


IMPAIRMENT






PTEN
CANCER
GACCAACGGCT
TGA
VQR-BE3
W111R
MC116




AAGTGAAGA









PIK3CA
CANCER
TCCTTTCTTCA
ACTGGT
SAKKH-BE3
K111R
CRL-5853




CGGTTGCCT









PIK3CA
CANCER
CTCCTGCTCAG
AGA
VQR-BE3
Q546R
CRL-2505




TGATTTCAG









TP53
CANCER
TGTCACACATG
TGG
YEE-BE3
N239D
SNU475




TAGTTGTAG









HRAS
CANCER
CCTCCCGGCCG
AGG
YEE-BE3
Q61R
MC/CAR




GCGGTATCC
















TABLE 6







Exemplary diseases that may be treated using base editors. 












gene
Base




Disease target
symbol
changed
sgRNA (PAM)
Base editor





Prion disease
PRNP
R37*
GGCAGCCGATACCCGGGGCA(GGG)
BE3





GGGCAGCCGATACCCGGGGC(AGG)






Pendred syndrome
Slc26a4
c.919-2A>G
TTATTGTCCGAAATAAAAGA(AGA)
BE3





ATTGTCCGAAATAAAAGAAG(AGG)
(VQR SaCas9)





TTGTCCGAAATAAAAGAAGA(GGA)






GTCCGAAATAAAAGAAGAGGAAAA(AAT)






GTCCGAAATAAAAGAAGAGGAAAAA(ATT)






Congenital 
Tmc1
c.545A>G
CAGGAAGCACGAGGCCACTG(AGG)
BE3


deafness


AACAGGAAGCACGAGGCCAC(TGA)
YE-BE3





AGGAAGCACGAGGCCACTGA(GGA)
YEE-BE3





Acquired 
SNHL
S33F
TTGGATTCTGGAATCCATTC(TGG)
BE3


deafness









Alzheimer's 
APP
A673T
TCTGCATCCATCTTCACTTC(AGA)
BE3 VQR


Disease









Niemann-Pick 
NPC1
I1061T
CTTACAGCCAGTAATGTCAC(CGA)
BE3 VQR


Disease Type C





The protospacer and PAM sequences are shown in the sgRNA (PAM) column.


The PAM sequence is shown in parentheses and with the base to be edited indicated by underlining.






Additional exemplary genes in the human genome that may be targeted by the base editors or complexes of this disclosure are provided herein in Tables 7 and 8. Table 7 includes gene mutations that may be corrected by changing a cytosine (C) to a thymine (T), for example, using a BE3 nucleobase editor. Table 8 includes gene mutations that may be corrected by changing a guanine (G) to an adenine (A), for example, using a BE3 nucelobase editor.










Lengthy table referenced here




US12344869-20250701-T00001


Please refer to the end of the specification for access instructions.














Lengthy table referenced here




US12344869-20250701-T00002


Please refer to the end of the specification for access instructions.






REFERENCES



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EQUIVALENTS AND SCOPE

Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents of the embodiments described herein. The scope of the present disclosure is not intended to be limited to the above description, but rather is as set forth in the appended claims.


Articles such as “a,” “an,” and “the” may mean one or more than one unless indicated to the contrary or otherwise evident from the context. Claims or descriptions that include “or” between two or more members of a group are considered satisfied if one, more than one, or all of the group members are present, unless indicated to the contrary or otherwise evident from the context. The disclosure of a group that includes “or” between two or more group members provides embodiments in which exactly one member of the group is present, embodiments in which more than one members of the group are present, and embodiments in which all of the group members are present. For purposes of brevity those embodiments have not been individually spelled out herein, but it will be understood that each of these embodiments is provided herein and may be specifically claimed or disclaimed.


It is to be understood that the invention encompasses all variations, combinations, and permutations in which one or more limitation, element, clause, or descriptive term, from one or more of the claims or from one or more relevant portion of the description, is introduced into another claim. For example, a claim that is dependent on another claim can be modified to include one or more of the limitations found in any other claim that is dependent on the same base claim. Furthermore, where the claims recite a composition, it is to be understood that methods of making or using the composition according to any of the methods of making or using disclosed herein or according to methods known in the art, if any, are included, unless otherwise indicated or unless it would be evident to one of ordinary skill in the art that a contradiction or inconsistency would arise.


Where elements are presented as lists, e.g., in Markush group format, it is to be understood that every possible subgroup of the elements is also disclosed, and that any element or subgroup of elements can be removed from the group. It is also noted that the term “comprising” is intended to be open and permits the inclusion of additional elements or steps. It should be understood that, in general, where an embodiment, product, or method is referred to as comprising particular elements, features, or steps, embodiments, products, or methods that consist, or consist essentially of, such elements, features, or steps, are provided as well. For purposes of brevity those embodiments have not been individually spelled out herein, but it will be understood that each of these embodiments is provided herein and may be specifically claimed or disclaimed.


Where ranges are given, endpoints are included. Furthermore, it is to be understood that unless otherwise indicated or otherwise evident from the context and/or the understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value within the stated ranges in some embodiments, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise. For purposes of brevity, the values in each range have not been individually spelled out herein, but it will be understood that each of these values is provided herein and may be specifically claimed or disclaimed. It is also to be understood that unless otherwise indicated or otherwise evident from the context and/or the understanding of one of ordinary skill in the art, values expressed as ranges can assume any subrange within the given range, wherein the endpoints of the subrange are expressed to the same degree of accuracy as the tenth of the unit of the lower limit of the range.


In addition, it is to be understood that any particular embodiment of the present invention may be explicitly excluded from any one or more of the claims. Where ranges are given, any value within the range may explicitly be excluded from any one or more of the claims. Any embodiment, element, feature, application, or aspect of the compositions and/or methods of the invention, can be excluded from any one or more claims. For purposes of brevity, all of the embodiments in which one or more elements, features, purposes, or aspects is excluded are not set forth explicitly herein.










LENGTHY TABLES




The patent contains a lengthy table section. A copy of the table is available in electronic form from the USPTO web site (). An electronic copy of the table will also be available from the USPTO upon request and payment of the fee set forth in 37 CFR 1.19(b)(3).





Claims
  • 1. A complex comprising: (i) a Cas9 protein;(ii) a cytidine deaminase;(iii) a uracil glycosylase inhibitor (UGI) protein; and(iv) a guide RNA (gRNA);wherein the complex deaminates a cytidine in a target nucleic acid sequence.
  • 2. The complex of claim 1, wherein the Cas9 protein is a Cas9 nickase (nCas9).
  • 3. The complex of claim 2, wherein the nCas9 comprises an amino acid sequence having at least 85% sequence identity to the amino acid sequence provided in SEQ ID NO: 10, and wherein the amino acid sequence provided in SEQ ID NO: 10 further comprises a D10A mutation, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, and 4273-4276.
  • 4. The complex of claim 2, wherein the nCas9 comprises one or more of N497A, R661A, Q695A, or Q926A mutations in the amino acid sequence provided in SEQ ID NO: 10, or one or more corresponding mutations in any of the amino acid sequences provided in SEQ ID NOs: 11-260, and 4273-4276.
  • 5. The complex of claim 1, wherein the Cas9 protein is a nuclease-inactive Cas9 (dCas9).
  • 6. The complex of claim 5, wherein the dCas9 comprises an amino acid sequence having at least 85% sequence identity to the amino acid sequence provided in SEQ ID NO: 10, and wherein the amino acid sequence provided in SEQ ID NO: 10 further comprises a D10A mutation, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-26, and 4273-4276.
  • 7. The complex of claim 6, wherein the dCas9 comprises an H840A mutation in the amino acid sequence provided in SEQ ID NO: 10, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 11-260, and 4273-4276.
  • 8. The complex of claim 5, wherein the dCas9 comprises one or more of N497A, R661A, Q695A, or Q926A mutations in the amino acid sequence provided in SEQ ID NO: 10, or one or more corresponding mutations in any of the amino acid sequences provided in SEQ ID NOs: 11-260, and 4273-4276.
  • 9. The complex of claim 1, wherein the Cas9 protein is selected from the group consisting of a Staphylococcus aureus Cas9 protein (SaCas9), a nuclease inactive SaCas9 (dSaCas9), a SaCas9 nickase (nSaCas9), a Streptococcus pyrogenes Cas9 protein (SpCas9), a nuclease inactive SpCas9 (dSpCas9), and a SpCas9 nickase (nSpCas9).
  • 10. The complex of claim 9, wherein the SaCas9 comprises the amino acid sequence provided in SEQ ID NO: 4273 or 4274.
  • 11. The complex of claim 10, wherein the SaCas9 comprises one or more of E781K, N967K, or R1014H mutations in the amino acid sequence provided in SEQ ID NO: 4273, or one or more corresponding mutations in any of the amino acid sequences provided in SEQ ID NOs: 10-260 and 4274-4276.
  • 12. The complex of claim 9, wherein the SpCas9 comprises the amino acid sequence provided in SEQ ID NO: 4276.
  • 13. The complex of claim 9, wherein the SpCas9 comprises a D9A mutation in the amino acid sequence provided in SEQ ID NO: 4276, or a corresponding mutation in any of the amino acid sequences provided in SEQ ID NOs: 10-260, and 4273-4276.
  • 14. The complex of claim 1, wherein the Cas9 protein is derived from Corynebacterium ulcerous, Corynebacterium diphtheria, Spiroplasma syrphidicola, Prevotella intermedia, Spiroplasma taiwanense, Streptococcus iniae, Belliella baltica, Psychroflexus torquisI, Streptococcus thermophilus, Listeria innocua, Campylobacter jejuni, or Neisseria meningitidis.
  • 15. The complex of claim 14, wherein the Cas9 protein is derived from Neisseria meningitidis.
  • 16. The complex of claim 1, wherein the cytidine deaminase: (i) is an apolipoprotein B mRNA-editing complex (APOBEC) family deaminase;(ii) comprises an amino acid sequence that is at least 85% identical to any of the amino acid sequences of SEQ ID NO: 266-284, 607-610, 5724-5736, and 5738-5741;(iii) comprises any of the amino acid sequences of SEQ ID NO: 266-284, 607-610, 5724-5736, and 5738-5741;(iv) is a rat APOBEC1 (rAPOBEC1) deaminase comprising one or more mutations selected from the group consisting of W90Y, R126E, and R132E of SEQ ID NO: 284, or one or more corresponding mutations in another APOBEC deaminase;(v) is a human APOBEC1 (hAPOBEC1) deaminase comprising one or more mutations selected from the group consisting of W90Y, Q126E, and R132E of SEQ ID NO: 5724, or one or more corresponding mutations in another APOBEC deaminase;(vi) is a human APOBEC3G (hAPOBEC3G) deaminase comprising one or more mutations selected from the group consisting of W285Y, R320E, and R326E of SEQ ID NO: 275, or one or more corresponding mutations in another APOBEC deaminase;(vii) is an activation-induced deaminase (AID); or(viii) is a cytidine deaminase 1 from Petromyzon marinus (pmCDA1).
  • 17. The complex of claim 1, wherein the cytidine deaminase is a cytidine deaminase from a human or a rat.
  • 18. The complex of claim 16, wherein the APOBEC family deaminase is selected from the group consisting of APOBEC1 deaminase, APOBEC2 deaminase, APOBEC3A deaminase, APOBEC3B deaminase, APOBEC3C deaminase, APOBEC3D deaminase, APOBEC3F deaminase, APOBEC3G deaminase, and APOBEC3H deaminase.
  • 19. The complex of claim 16, wherein the APOBEC family deaminase is an APOBEC3G deaminase.
  • 20. The complex of claim 1, wherein the UGI protein comprises an amino acid sequence that is at least 85% identical to any one of SEQ ID NOs: 322-324 and 600.
  • 21. The complex of claim 1, wherein the UGI protein comprises an amino acid sequence set forth in any one of SEQ ID NOs: 322-324 and 600.
  • 22. The complex of claim 1, wherein the gRNA comprises a nucleotide sequence of at least 10 contiguous nucleotides that is complementary to the target nucleic acid sequence.
  • 23. The complex of claim 1, wherein the gRNA is from 15-100 nucleotides long.
  • 24. The complex of claim 1, wherein the target nucleic acid sequence is a DNA sequence.
  • 25. The complex of claim 1, wherein the target sequence is in the genome of a eukaryote.
  • 26. The complex of claim 25, wherein the eukaryote is a mammal.
  • 27. The complex of claim 26, wherein the mammal is human.
  • 28. The complex of claim 1, wherein the target nucleic acid sequence comprises a sequence associated with a disease or disorder, and wherein the deamination of the cytidine results in a sequence that is not associated with the disease or disorder.
  • 29. A method of nucleic acid editing, the method comprising contacting a target nucleic acid molecule with the complex of claim 1, wherein the method results in deamination of a cytidine in the target nucleic acid molecule.
  • 30. The method of claim 29, wherein the gRNA comprises a nucleotide sequence of at least 10 contiguous nucleotides that is complementary to the target nucleic acid molecule.
  • 31. The method of claim 29, wherein the target nucleic acid molecule comprises a sequence associated with a disease or disorder, and wherein the deamination of the cytidine results in a sequence that is not associated with the disease or disorder.
  • 32. The method of claim 29, wherein the target nucleic acid molecule comprises a point mutation associated with a disease or disorder, and wherein the deamination corrects the point mutation.
  • 33. The method of claim 32, wherein the target nucleic acid molecule comprises a T to C point mutation, and wherein the deamination of the mutant C base results in a nucleic acid sequence that is not associated with the disease or disorder.
  • 34. The method of claim 31, wherein the target nucleic acid sequence associated with the disease or disorder encodes a protein and wherein the deamination introduces a stop codon into the sequence associated with the disease or disorder, resulting in a truncation of the encoded protein.
RELATED APPLICATIONS

This application is a continuation of and claims priority under 35 U.S.C. § 120 to U.S. application, U.S. Ser. No. 15/960,171, filed Apr. 23, 2018, which is a continuation of and claims priority under 35 U.S.C. § 120 to international PCT Application, PCT/US2016/058344, filed Oct. 22, 2016, and is a continuation of and claims priority under 35 U.S.C. § 120 to U.S. application, U.S. Ser. No. 15/331,852, filed Oct. 22, 2016, which claims priority under 35 U.S.C. § 119(e) to U.S. provisional patent applications, U.S. Ser. No. 62/245,828 filed Oct. 23, 2015, U.S. Ser. No. 62/279,346 filed Jan. 15, 2016, U.S. Ser. No. 62/311,763 filed Mar. 22, 2016, U.S. Ser. No. 62/322,178 filed Apr. 13, 2016, U.S. Ser. No. 62/357,352 filed Jun. 30, 2016, U.S. Ser. No. 62/370,700 filed Aug. 3, 2016, U.S. Ser. No. 62/398,490 filed Sep. 22, 2016, U.S. Ser. No. 62/408,686 filed Oct. 14, 2016, and U.S. Ser. No. 62/357,332 filed Jun. 30, 2016; each of which is incorporated herein by reference. This application contains a Sequence Listing which has been submitted in ASCII format via EFS-Web and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Nov. 9, 2021, is named H082470213US10-SEQ-EPG and is 4,463,178 bytes in size.

GOVERNMENT SUPPORT

This invention was made with Government support under grant number EB022376 (formerly GM065400) awarded by the National Institutes of Health. The Government has certain rights in the invention.

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Related Publications (1)
Number Date Country
20220220462 A1 Jul 2022 US
Provisional Applications (9)
Number Date Country
62408686 Oct 2016 US
62398490 Sep 2016 US
62370700 Aug 2016 US
62357332 Jun 2016 US
62357352 Jun 2016 US
62322178 Apr 2016 US
62311763 Mar 2016 US
62279346 Jan 2016 US
62245828 Oct 2015 US
Continuations (3)
Number Date Country
Parent 15960171 Apr 2018 US
Child 17527011 US
Parent 15331852 Oct 2016 US
Child 15960171 US
Parent PCT/US2016/058344 Oct 2016 WO
Child 15960171 US